Ladies, when your three important sex hormone levels are ideal:

  • Estrogen – You feel like you again! Your skin glows, your mind clears, and sensuality returns.
  • Progesterone – Your “PMS dragon” disappears, sleep is sweet, and emotions stabilize. You wake up happy. You feel calm again, cravings diminish, and you feel in harmony with yourself and others.
  • Testosterone – Your self-confidence and strength are back, energy and zest for life returns, libido improves, focus and memory restores, weight is easier to manage, and there’s a spring in your step.

Remember men, when your important sex hormone levels are ideal:

  • Testosterone – Self-confidence and muscle strength returns, improved energy and zest for life, improved sex drive, improved endurance, lose belly fat, and sureness in your stride.
  • Progesterone – Sleep improves, emotions stabilize. You wake up happy. You feel calm, cravings leave, and you feel in harmony with yourself and others.

Don’t give up! You can feel like yourself again. Promise. Taking the first step is always the hardest. And we are here for you every step of the way…

Library and Articles: Show me the Science…

Hormone Imbalance: Impact on Your Daily Life

Overview: This article outlines how hormones impact how you feel, and identifies some key physical and mental symptoms that indicate an imbalance.

What are hormones, anyway?

Hormones act like a key that fits into a lock. They are natural chemical “messengers” that are made naturally in our bodies. They travel through our blood streams to communicate to our bodies what they should do (1).

There are three important reproductive hormones:

  • Estrogen
  • Progesterone
  • Testosterone

Signs of Hormone Imbalance

Menopausal hormone imbalance symptoms are often related to changing levels of estrogen, progesterone, and testosterone. Each woman’s body responds to the process of hormone deficiency and imbalance in its own unique way.

Estrogen
Estrogen fluctuates frequently throughout most women’s lives. Common complaints of unbalanced or low estrogen are:

  • Hot flashes
  • Night sweats
  • Memory loss
  • Fatigue
  • Dry skin
  • Loss of sensuality
  • Vaginal dryness
  • Painful sex
  • Not feeling “like yourself”

Estrogen may also help protect against heart disease (2) and osteoporosis (3).

Progesterone
Progesterone is often called the “happy hormone” or the “hormonal harmonizer,” helping to balance estrogen, and stabilize moods. Common symptoms of unbalanced or low progesterone are:

  • Irregular periods
  • Light or heavy flow
  • Irritability
  • Sleep disturbances
  • Cramps
  • Bloating
  • Water retention
  • Weight gain
  • Overwhelming sadness
  • Feelings of nervousness
  • Heart palpitations
  • Headaches

Natural progesterone also helps raise good cholesterol (4), helps protect the brain (5), and helps protect the breast tissue against breast cancer (6).

Testosterone
Testosterone is present in smaller amounts in women’s bodies compared to men’s. It plays an important role in our overall wellness. Common complaints of unbalanced or low testosterone are:

  • Weight issues
  • Muscle loss
  • Fatigue
  • Low sex drive
  • Short-term memory loss
  • Problems with focus and concentration
  • Low self-confidence
  • General loss of zest and vitality

Low testosterone has also been linked to migraine headaches (7), fibrocystic disease (8), and bladder incontinence (9). It plays a role in preventing osteoporosis (10), cardiovascular disease (11), atherosclerosis (12), and diabetes (13).

Let’s Recap
Many women may not even notice that they have begun to experience a natural decline or hormone imbalance. Signs begin gradually over time, and include:

  • Varying cycle lengths
  • Changes in heaviness of periods
  • Intensified PMS symptoms
  • Mood changes
  • Loss of sex drive
  • Trouble sleeping

Women often write off these hormone imbalance symptoms as the result of stress, grief, or illness. However, as hormone imbalance or decline worsens, the symptoms often grow worse as well.

While you may feel like you’re alone or “going crazy,” your feelings are more common than you realize!

Right now, women all over the world are experiencing the same thoughts, feelings, and sensations that you are.

References
  1. National Institutes of Health – Medline Plus. “Hormones.” http://www.nlm.nih.gov/medlineplus/hormones.html.
  2. American Heart Association. “Menopause and Heart Disease.” http://www.heart.org/HEARTORG/Conditions/More/MyHeartandStrokeNews/Men opause-and-Heart-Disease_UCM_448432_Article.jsp.
  3. Mayo Clinic. “Osteoporosis Risk Factors.” http://www.mayoclinic.org/diseases-conditions/osteoporosis/basics/risk-factors/CON-20019924.
  4. Clinica Chimica Acta. Volume 115, Issue 1, p63-71. “Reduction of plasma high-density lipoprotein2 cholesterol and increase of postheparin plasma hepatic lipase activity during progestin treatment.” http://www.sciencedirect.com/science/article/pii/0009898181901078.
  5. Experimental Neurology. Volume 178, Issue 1, p59-67. “Progesterone Protects against Necrotic Damage and Behavioral Abnormalities Caused by Traumatic Brain Injury.” http://www.sciencedirect.com/science/article/pii/S0014488602980209.
  6. Breast Cancer Research and Treatment. Volume 8, Issue 3, p179-188. “Antiestrogen action of progesterone in breast tissue.” http://link.springer.com/article/10.1007/BF01807330.
  7. Headache. Volume 46, Issue 6, p925-933. “Testosterone replacement therapy for treatment refractory cluster headache.” http://www.ncbi.nlm.nih.gov/pubmed/16732838.
  8. Gynecological Endocrinology. Volume 28, Issue 6, p468-471. “Is hyperandrogenemia protective for fibrocystic breast disease in PCOS?” http://www.ncbi.nlm.nih.gov/pubmed/22103710.
  9. Maturitas. Volume 68, Issue 4, p355-361. “Beneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS.)” http://www.sciencedirect.com/science/article/pii/S0378512210004482.
  10. Hormone Research in Pediatrics. Volume 19, Number 1, p18-22. “Osteoporosis and Decline of Gonadal Function in the Elderly Male.” http://www.karger.com/Article/Abstract/179855.
  11. American Journal of Epidemiology. Volume 146, Issue 8, p 609-617. “Longitudinal Relation between Endogenous Testosterone and Cardiovascular Disease Risk Factors in Middle-aged Men.” http://aje.oxfordjournals.org/content/146/8/609.short.
  12. Journal of Internal Medicine. Volume 259, Issue 6, p576-582. “Low testosterone levels are associated with carotid atherosclerosis in men.” http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2006.01637.x/full.
  13. European Journal of Endocrinology. Issue 154, p899-906. “Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.” http://www.eje-online.org/content/154/6/899.short.

Depression: Why Do I Feel This Way?

Sir Winston Churchill described depression as a “big black dog” that followed him around. People who have turned to MEDSTUDIO seeking relief have shared that before therapy…

  • “I feel hopeless.”
  • “I felt sad all the time and just don’t feel like myself.”
  • “I don’t enjoy doing any of the things I usually love to do.”
  • “I’ve been having a lot of trouble sleeping lately.”
  • “Sometimes I feel like my life is not worth living anymore.”
  • “I feel so indecisive that I can’t make any decisions.”
  • “I have a great life, but the joy is missing.”
  • “I just feel so worthless.”

Such comments sometimes may point toward clinical depression, but there may be a number of reasons, prompting the “depression.”  Understanding the origin may give better clarity to appropriate treatments.

Of course, any time you have feelings of extreme sadness or anger that makes you feel as though you want to harm yourself or others, immediately seek professional help.

One reason for depression may be a lack of serotonin, a chemical in the brain.  For this chemical imbalance, classically trained providers might prescribe an SSRI (selective serotonin reuptake inhibitor) such as Paxil or Prozac.  SSRI’s provide treatment for a lack of serotonin in the synapses of the brain, but doesn’t provide the reason why one has this deficiency.  While it might be possible the person may have inherited this condition and they may benefit from this kind of treatment, it might be just as possible that symptoms of depression may not be the result of a serotonin deficiency but something else.

Depression And Your Unique Situation

Another reason for depression may be a major emotional trauma such as a loss of a loved one or a big change in one’s health. Loneliness and other difficult life situations are usually explainable and justifiable. But these depressive periods tend to exist for a relatively short time. Many people over time will learn to adjust to their losses. This person suffering from this type of depression may benefit from a short course of medication. The danger comes when the body becomes dependent on the medication and has withdrawals when trying to discontinue it.

Another real possibility is the person may be suffering from a loss or deficiency of hormones. 
Some experts believe this reason is far more common than classic clinical depression.
If your depression began during puberty or after age 30 when it is usual for hormones to start to decline, the root cause may be hormone-related.  Unfortunately, a hormonal imbalance is not often recognized medical professionals as the cause and in many of these cases, the person is told he/she has depression and the only treatment is an anti-depressant for which the rationale may not be found.

Frequently our patients will relate to us that they told their doctor they were not depressed, but rather they felt in despair or loss of joy which is not the same.   Over time they realized “things were just not right.” Reluctantly, they take the anti-depressant prescribed because they just want to get out of the funk or get unstuck.  Problems come when the side effects from their medication begin. The most common side effects of anti-depressants are weight gain, loss of sex drive, an inability to achieve an orgasm, and the loss of feelings of elation as well as those of sadness.  We hear people say, “I feel nothing – like I’m in neutral.”  Often these negative consequences of SSRIs are the actual reasons they sought help from the doctor in the first place.  It is not uncommon for patients to stop reporting these negative consequences to their doctors because they “become accustomed” to life without interest in sex or to the feeling of sadness they have.

Female testosterone deficiency may cause loss of energy and muscle, decreased sex drive, depression, and weight gain. Lack of progesterone may cause mood changes and poor sleep.  When estrogen is low or missing, the brain may be affected causing depression, poor memory and other symptoms.

Interested in learning more? 

Of course, information is great when evaluating and learning about your health choices.  Ultimately, only a licensed trained medical professional can make a qualified diagnosis and recommendation.  While this information is not to be used to diagnose, treat or cure any type of illness or health condition, we hope it will make you interested enough to seek more information and getting your life back. Most importantly – it’s Your Health. Your Choice. Your Journey.  We are here to guide you.  

When Your Doctor Doesn’t Have All the Answers

Overview: This article outlines when and where to seek advice when suffering from symptoms with possible hormone imbalance, as well as common misdiagnoses and related symptoms.

When to Seek Advice

For women considering hormone imbalance treatment, most start with a family doctor or medical provider. In some cases, they might visit a mental health provider. Unfortunately, many of these experts may not be trained to correctly diagnose and successfully administer the necessary treatment. Despite the best intentions, there is a good chance they received little, if any, education in school on this topic.

Here the Nurse Practioners at Med Studio have focused their careers on hormones & natural hormone therapy, and are dedicated to helping women (and the men who love them) find natural solutions to help guide you through menopause.

MedStudio offers natural therapies for people with unbalanced hormones, and frees them to live instead of suffering with unmanaged symptoms.

Anti-Depressants and Menopause

In many cases, when women shares the following symptoms with their main health care provider, they are diagnosed with anxiety and depression.

  • Insomnia
  • Night sweats
  • Loss of enthusiasm
  • Loss of sex drive
  • Sudden and unprecedented anxiety
  • Short temper
  • Panic attacks

(Sadly, some of the most commonly recommended anti-depressants often lower a woman’s sex drive and may actually stop your body’s ability to have an orgasm.)

Many women are given an anti-depressant or anti-anxiety medication to treat hot flashes. While recent studies have shown this kind of hormone imbalance treatment effective in reducing hot flashes, the medication doesn’t help what’s causing the symptoms in the first place.

Why Synthetic Hormones Are Used

Often when women take these symptoms to their gynecologist, they are told to take synthetic hormones like birth control or Premarin.

This may happen because classically trained physicians or providers receive little or no education on natural hormone therapy or alternative solutions in school.

(For some women these synthetic hormones are a good option but may treat only a portion of the symptoms. For others, they may cause unwanted problems down the road.)

Your Options

At MedStudio, asking your body the right questions helps your provider give you options and a solution that’s right for you!

Resources
Journal of Clinic Psychopharmacology. Volume 6, Issue 3. “Effects of Antidepressant Medication on Sexual Function: A Controlled Study.” http://journals.lww.com/psychopharmacology/abstract/1986/06000/effects_of _antidepressant_medication_on_sexual_.4.aspx.
The Lancet. Volume 356, Issue 2947, p2059-2063. “Venlafaxine in management of hot flashes in survivors of breast cancer: a randomized controlled trial.” http://www.sciencedirect.com/science/article/pii/S0140673600034036<.

Am I Ever Going to Feel Normal Again?

Overview: Real women and real stories about how natural hormone therapy changed their lives.

The answer to this commonly asked question is a resounding yes! Natural hormone therapy for menopause may help you love your life again.

As a result, you may restore your relationships, advance your career, and feel like yourself again with natural hormone therapy for menopause.

A New Woman

“When I first began natural hormone therapy, I was an angry, depressed woman on the war path. I needed help. If this was what life was going to be like, I was going to be done. Within weeks of beginning natural hormone therapy, my depression was going away, the anger was disappearing, and I was finding joy in my life again. I was happy to get up every morning and experience happiness again. My romance with my husband came back and it has never been so passionate. My husband was so impressed with what it did for me that he starting coming for treatments too. Life is good again!” – K. S.

Remember, when your three important hormone levels are ideal:

  • Estrogen – You feel like you again! Your skin glows, your mind clears, and sensuality returns.
  • Progesterone – Your “PMS dragon” disappears, sleep is sweet, and emotions stabilize. You wake up happy. You feel calm again, cravings diminish, and you feel in harmony with yourself and others.
  • Testosterone – Your self-confidence and strength are back, energy and zest for life returns, libido improves, focus and memory restores, weight is easier to manage, and there’s a spring in your step.

With all this to gain, what do you have to lose (except your sleepless nights and those pesky hot flashes?)

Husband Has His Girlfriend Back

“I love natural hormone therapy because I truly believe it saved my life! Before I started treatments, I was very depressed. Doctors had me on high doses of depression medicine. I seemed to get worse. I was to the point that I did not want to be here anymore. The last straw for me was to try natural hormone therapy, and I am now off of the depression medication. My sex life returned. My husband said he has his girlfriend back, and I have my life back!” – J. H.

Many women who’ve used natural hormone therapy during menopause have restored their relationships with their spouses and families, advanced their careers, and gained a renewed passion for life and all it has to offer.

Don’t give up!

You can feel like yourself again. Promise.

Taking the first step is always the hardest. And we are here for you every step of the way.

Many women who utilize natural hormone therapy for menopause have restored their relationships with their spouses and families, advanced their careers, and gained a renewed passion for life and all it has to offer.

Migraines & Your Hormones

Everyone ages and you start to lose your natural hormone levels.

The reduction of the 3 main hormones Estrogen, Progesterone, and Testosterone in women and Testosterone in men can cause a lot of symptoms affecting your health and the way you feel.

There are a variety of types of headaches including:

1) Migraines with or without Aura

2) Cluster

3) Tension

4) Trigeminal Neuralgia

5) Proximal Hemicranial

6) Post Herpetic Opthalmicus

7) Occipital Neuralgia

8) Atypical Facial Pain

9) Secondary and Other Headaches

Many have said, “I could deal with the headache if it was minor and ‘one & done.’” And for many people, the long term effects and disruption to life is overwhelming.

The American Migraine Study II ( which had almost 4,000 migraine sufferers help in the study) shows that migraines were most prevalent in:

  • People between the ages of 35 and 55
  • 91% miss work or can’t function normally during migraine attack
  • 70% of all migraine sufferers are women
  • 69% have consulted a physician at some time seeking treatment for migraine pain
  • 63% have one or more migraine attacks monthly
  • 59% missed family or social events
  • 51% said migraines cut in half their work or school productivity
  • Almost half of all migraine sufferers are have not been diagnosed
  • 49%  said they had to restrict activities for at least one day during a migraine episode
  • 47% of people who have symptoms that meet the guidelines to be diagnosed with migraines thought they had a tension headache, sinus headache or another type of headache
  • 25% have one or more migraines a week
  • 24% have gone to the emergency room because the migraine pain was so severe

This study and numbers show migraines are not rare.

So, why do they happen?

Hormones and Migraines

Since the 1960’s there’s been a connection between certain hormone imbalances and migraines.1 Estrogen has been prescribed in various forms for the treatment of menopausal hormones. Many times, people don’t see the pattern and connect hormones and migraines. Women and even men should not have to suffer in silence.

And of course, information is great when evaluating and learning about your health choices. Ultimately, only a qualified licensed medical provider can make a qualified diagnosis and recommendation.   While this document is not to be used to diagnose, treat or cure any type of illness or health condition, we hope it will make you interested enough to seek more information and get your life back. After all, it’s Your Health. Your Choice. Your Journey.  We are here to guide you.

Want to learn more? 

If you have symptoms and want relief, call or email MedStudio today to schedule your 30 minute free no obligation consult to learn more about how we can help you feel better.

1 http://www.webmd.com/migraines-headaches/guide/hormones- headaches

Perimenopause vs. Menopause

Overview: This article describes the difference between perimenopause and menopause.

Common Symptoms of Menopause

The most common symptoms of menopause indicating its onset often present themselves in ways that may not immediately call that condition to mind. It is important to pay careful attention to the body when one experiences any of these signs of symptoms.

Women report hundreds of symptoms related to perimenopause and menopause. Here are the 22 most commonly reported symptoms of menopause:

  1. Hot flashes
  2. Night sweats
  3. Dry skin
  4. Vaginal dryness and/or painful sex
  5. Chronic fatigue
  6. Restless legs
  7. Hair loss
  8. Sleep issues
  9. Depression or loss of joy
  10. Irritability
  11. Anxiety or nervousness
  12. Mood swings
  13. Migraine headaches
  14. Palpitations
  15. Fatigue
  16. Weight control issues
  17. Low sex drive
  18. Poor focus
  19. Memory lapses
  20. Decreased exercise tolerance
  21. Loss of muscle tone
  22. Body and joint pain

Stages of Menopause

Menopause is a normal part of life, just like puberty. Many women may notice changes in their bodies before and after menopause. The transition usually has three parts:

  1. Perimenopause
  2. Menopause
  3. Post-Menopause

Changes usually begin with perimenopause. This can begin several years before a woman’s last menstrual period. Menopause comes next, the end of the menstrual periods. After a full year without a period, menopause is over. Post-menopause follows menopause and lasts for the rest of a woman’s life. The average age for the last period is 51. Some women, however, have the last period in their forties, and some have it later in their fifties (1). For many women, this process is a smooth transition and goes unnoticed with no symptoms, but for others this seemingly normal part of life is not normal for them at all.

Premature Menopause

Be reassured that barring an underlying medical condition that sets off premature menopause, the age when perimenopause begins is simply individual to your own body. The symptoms of menopause during this time vary for every woman.

MedStudio offers natural therapies for people with unbalanced hormones, and frees them to live instead of suffering with unmanaged symptoms.

References
  1. National Institutes of Health – National Institute on Aging, “Menopause.” http://www.nia.nih.gov/health/publication/menopause.

Mood Swings

Ah, mood swings… for some women, hormones seem to have only a small impact on their moods. For others, a literal train wreck looms at every turn.

“Women can be… greatly affected by hormone fluctuations. Sometimes it gets to the point of feeling totally overwhelmed – as if for a time they have lost control of their life.” – Christiane Northrup, MD author of “The Wisdom of Menopause”

Ladies, your brain is an amazingly sensitive organ! It weighs about 3 pounds on average and uses 20% of your glucose, oxygen and nutrients of your body. It communicates with and is the command center of your entire body. Communication is done by neurons via neurotransmitters.

What happens when the neurotransmitters don’t get the help they need from dietary intake, body chemistry or hormones? They misfire, or don’t fire as often as they should. This can lead to those moods, depression, or conditions like anxiety. Well, conventionally, you’ll probably be told you need anti-depressants, neuroleptics, anti-anxiety medications…But, the problem may not be that you are broken mentally.

It is possible the issue is your unbalanced hormone levels.

Moods & Your Hormones

The word “hormone” is from the Greek meaning to rouse or set in motion. It is a messenger or sorts calling certain parts of your body to action. What happens if the messenger stops doing its job? Do you treat the part of your body that didn’t get the message, or do you try to get the messenger back to work?

Did you know your thyroid hormone is related to serotonin in your body? You’ve probably heard of Serotonin. Serotonin is one of the primary ingredients of anti-depressant medications. Serotonin is called the “happy” hormone. It helps to regulate mood and positive feelings, like being in love.

Did you know why women with estrogen deficiency once did not need anti-depressants to regulate their moods, and suddenly now they do?

Because estrogen is a natural serotonin reuptake inhibitor (SSRI). Here’s a secret – it’s nature’s anti – depressant! Does it make more sense to replace the natural function that served you so well for years, or to return that function to your body naturally? Estrogen deficiency has a domino effect on brain chemistry and moods.

Do you feel sometimes like you just don’t want to talk to people? (P.S. You aren’t alone.) Another important precursor hormone to estradiol and testosterone is the unsung hero DHEA. This messenger helps regulate a sense of well- being, improved sleep as well as libido. DHEA also has the important job of increasing the firing activity of serotonin neurons (the happy ones!)

Progesterone – the unsung hero of hormones – is another important puzzle piece to your mood. The largest concentration of progesterone receptors is in what is called the limbic area of the brain, which is the center of emotion and also is called the “area of rage and violence” by animal physiologists. Progesterone has a calming effect on the brain, which means that an imbalance or deficiency can lead to varying levels of anxiety, depending on the level of the imbalance.

Books upon books have been written on hormones and the impact on your body, your moodiness, depression, and yes, even your anxiety. You are not alone… we promise. Information is power – and you should have all the power YOU need to make the right decisions for your health and happiness.

Bioidentical Progesterone versus Progestin: What’s the Difference?

Many medical researchers and healthcare practitioners debate the merits of bioidentical hormones (i.e., those that are chemically identical to the hormones produced naturally in the body) versus non-bioidentical ones. The primary concern with non-bioidentical treatments is that because they are not quite identical to the substances produced in the body, the body typically responds slightly differently, with a greater possibility of undesirable side effects.

Dr. Bronson reports that the primary biochemical difference between bioidentical progesterone and non-bioidentical progestins is their relationship with water. Bioidentical progesterone is hydrophobic, meaning that it repels water or acts as a diuretic. In contrast, non-bioidentical progestin molecules are hydrophilic, meaning that they bond easily with water. So, if you take a non- bioidentical progestin such as Depo Provera®, your body (including your brain) can retain water, which may have additional side effects on your brain chemistry.

A study by Dr. Lorraine Fitzpatrick of the Mayo Clinic supports the finding that perimenopausal women reported better relief of anxiety and depressive symptoms with bioidentical progesterone than they did with a non-bioidentical progestin.

Women and even men should not have to suffer in silence. If you have symptoms and want relief, contact someone at MedStudio to find out more. And of course, information is great when evaluating and learning about your health choices. Ultimately, only a qualified licensed medical provider can make a qualified diagnosis and recommendation.   While this document is not to be used to diagnose, treat or cure any type of illness or health condition, we hope it will make you interested enough to seek more information and get your life back. After all, it’s Your Health. Your Choice. Your Journey.  We are here to guide you.

Want to learn more? 

If you have symptoms and want relief, call or email MedStudio today to schedule your 30 minute free no obligation consult to learn more about how we can help you feel better.
_____

Sources:

“Mood Biochemistry of Women at Mid-Life” by Phyllis J. Bronson, PhD; presented at the American Academy of Environmental Medicine Conference, September 28–October 1, 2000, in Hilton Head, SC; and personal interviews, February 2001 and February 2012.

“Comparison of Regimens Containing Oral Micronized Progesterone or Medroxyprogesterone Acetate on Quality of Life in Postmenopausal

Women: A Cross-Sectional Survey” by Lorraine A. Fitzpatrick, MD, Cindy Pace, BS, and Brinda Wiira, PhD; Journal of Women’s Health & Gender- Based Medicine, Volume 9, Number 6, 2000.

Sleep & Your Hormones

As we age, all of us begin to experience a reduction in our natural hormone levels. The reduction of the hormones Estrogen, Progesterone, and Testosterone in women and Testosterone in men can cause a lot of symptoms affecting your health and the way you feel.

Think you Have A Sleep Disorder?

If you think you might have a prolonged problem with sleep, you may need to see your medical provider  about having a sleep study performed. However, studies show women especially have greater problems going to sleep and staying asleep than most men.1

When hormone levels are normal as they were when you were younger, sleep under normal conditions usually isn’t a problem. As your body ages, sleep may become a huge problem, because important natural hormone amounts get lower as we age naturally. Many people try sleep medications such as Ambien, or to an antidepressant such as Lexapro, Cymbalta, Celexa, Prozac, or Paxil. Daytime drowsiness and other major side effects should be carefully considered when weighing treatment options. Women who have trouble sleeping experience daytime sleepiness, an increased accident rate, difficulty concentrating, and the effects can be seen in their performance on their jobs or in school.

You don’t feel like you did before, and may think that a good night’s sleep is a thing of the past. Many people self  report going to bed and finally sleeping for an hour, then waking up unable to return to sleep. (Might even get up and watch TV or read a book waiting for sleep to return. Does this sound familiar – checking Facebook in the middle of the night?) Miserable, and unable to sleep, you might toss and turn in bed and sleep for two or three hours only to find yourself wide awake again.

Tossing and turning all night, you finally give up trying to sleep – ending up frustrated, angry and tired – all hours before your alarm clock even goes off.

Many of our patients have self reported on how their sleep patterns have improved since being on natural hormone therapy.

“I  felt  rested when I woke in the morning.”

“Since I have been on hormone therapy I have had the best night sleep in 5 years.”

“I can sleep at night since beginning hormone therapy.”

Sleep disturbances are much more common during perimenopause, the time leading up to menopause, and after menopause until the natural hormones are replaced. Night sweats (hot flashes at night) may interrupt sleep throughout the night.

Progesterone is an important hormone that helps women sleep. By age 35, women will begin to lose progesterone (made in the ovaries) especially during the last half of the menstrual cycle. Estradiol (a form of estrogen) also affects the brain and how we sleep. When these two essential hormones are replaced naturally, many people find they sleep all night long and wake rested. Additionally, many of our patients with Restless Leg Syndrome have experienced relief of symptoms with the use of natural hormone therapy allowing them to sleep more soundly at night.

Interested in learning more?

Women (and even men) should not have to suffer in silence. If you have symptoms and want relief, contact someone at MedStudio to find out more. And of course, information is great when evaluating and learning about your health choices. Ultimately, only a qualified licensed medical provider can make a qualified diagnosis and recommendation.   While this document is not to be used to diagnose, treat or cure any type of illness or health condition, we hope it will make you interested enough to seek more information and get your life back. After all, it’s Your Health. Your Choice. Your Journey.  We are here to guide you.

1                       http://www.sleepfoundation.org/article/sleep-topics/women-and-sleep

Anxiety and Hot Flashes

Overview: This article describes the outcome of a study around anxiety and menopause.

Abstract Objective

To estimate the association of anxiety with menopausal hot flashes in the early transition to menopause.

Design

A randomly identified, population-based cohort of midlife women followed up for six years to assess reproductive hormones and other physical, emotional, and behavioral factors. At enrollment the women were premenopausal, aged 35 to 47 years, and had regular menstrual cycles in the normal range. Enrollment was stratified to obtain equal numbers of African American (n = 219) and white (n = 217) women.

Results

At the 6-year endpoint, 32% of the women were in the early transition stage and 20% reached the late menopausal transition or were postmenopausal. Reports of hot flashes increased with the transition stages, which were determined by bleeding patterns. At endpoint, hot flashes were reported by 37% of the premenopausal women, 48% of those in the early transition, 63% of women in the late transition, and 79% of the postmenopausal women. Anxiety scores were significantly associated with the occurrence of hot flashes and were also significantly associated with the severity and frequency of hot flashes (each outcome at P < 0.001). Compared with women in the normal anxiety range, women with moderate anxiety were nearly three times more likely to report hot flashes and women with high anxiety were nearly five times more likely to report hot flashes. Anxiety remained strongly associated with hot flashes after adjusting for menopause stage, depressive symptoms, smoking, body mass index, estradiol, race, age, and time. In a predictive model, anxiety levels at the previous assessment period and the change in anxiety from the previous assessment period significantly predicted hot flashes (P < 0.001).

Conclusions

Anxiety is strongly associated with menopausal hot flashes after adjusting for other variables including menopause stage, smoking, and estradiol levels. Anxiety preceded hot flashes in this cohort. Additional studies are needed to examine the duration of menopausal hot flashes and to determine whether treatments that target anxiety effectively reduce menopausal hot flashes.

Resources
National Center for Biotechnology Information (NCBI). http://www.ncbi.nlm.nih.gov/pubmed/15879914.

Yale Study: The High Cost of Hot Flashes

Overview: This article describes a Yale study done to research the high cost associated with vasomotor symptoms (VMS).

VMS Economic Impact

The steep decline in the use of hormone therapy has spawned a prevalent but preventable side effect: millions of women suffering in silence with hot flashes, according to a study by a Yale School of Medicine researcher and colleagues.

In the study the team found that moderate to sever hot flashes – also called vasomotor symptoms (VMS) – are not treated in most women. Women with VMS experience more than feeling hot. Other frequently occurring symptoms include fatigue, sleep disturbance, depression, anxiety, and impaired short-term memory.

“Not treating these common symptoms causes many women to drop out of the labor force at a time when their careers are on the upswing,” said Dr. Philip Sarrel, emeritus professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences, and Psychiatry. “This also places demands on healthcare and drives up insurance costs.”

Sarrel and colleagues used data on health insurance claims to compare over 500,000 women, half with and half without hot flashes. The team calculated the costs of healthcare and work loss over a 12-month period. Participants were all insured by Fortune 500 companies.

The team found that women who experienced hot flashes had 1.5 million more healthcare visits than women without hot flashes. Costs for the additional healthcare was $339,559,458. The cost of work lost was an additional $27,668,410 during the 12-month study period.

Hot flashes are the result of loss of ovarian hormones in the years just before and after natural menopause. For women who have a hysterectomy, symptoms may occur almost immediately following surgery, and are usually more sever and long-lasting. More than 70% of all menopausal women and more than 90% of those with hysterectomies experience VMSthat affect daily function.

In the past, hot flashes were readily treated with either hormone therapy or alternative approaches. However, following the 2002 publication of the findings in the Women’s Health Initiative study, there has been a sharp drop in the use of hormone therapy due to unfounded fears of cancer risks, according to Sarrel.

“Women are not mentioning it to their healthcare providers, and providers aren’t bringing it up,” said Sarrel. “The symptoms can be easily treated in a variety of ways, such as with low-dose hormone patches, non-hormonal medications, and simple environmental adjustments such as cooling the workplace.”

Other authors on the study include Dr. David Portman, Patrick Lefebvre, Marie-Helene Lafeuille, Amanda Meline Grittner, Jonathan Fortier, Jonathan Gravel, Mei Sheng Duh, and Dr. Peter M. Aupperle. The study was funded by Noven Pharmaceuticals.

References
Yale News. (2014). The high cost of hot flashes: Millions in lost wages preventable. http://news.yale.edu/2014/08/27/high-cost-hot-flashes-millions-lost-wages-preventable.

Hormone Therapy: Natural vs. Synthetic

Overview: This article clearly and simply outlines the primary differences between natural and synthetic hormones.

Rebuilding the Puzzle: Hormone Therapy

Today, with an overwhelming amount of information available right at our fingertips, there are thousands of articles focused on hormone therapy. The downside of all of this information is that the answers we need get lost, leaving us confused and frustrated.

So, lets break it down simply and clearly: What’s the difference between synthetic hormone therapy and natural hormone therapy?

Synthetic Hormone Therapy
Synthetic hormones are similar to the hormones that we naturally produce in our bodies, but they aren’t identical. Research indicates that synthetic hormones vary clinically in both safety and effectiveness, and when scientists look at a synthetic hormone on the molecular level, they can see that a part of it doesn’t match (1).

Simply put, synthetic hormones are similar to that puzzle piece that you think will fit perfectly, but one side just doesn’t match up correctly.

Natural Hormone Therapy
Natural hormones – sometimes referred to as “bio-identical” or “derived natural” – are different than synthetic hormones. Under a microscope, scientists can see that the chemical structure on the molecular level is an exact bio-identical match with the hormones produced in the human body (2); the piece fits in the puzzle perfectly.

It’s important to recognize that you live in your skin and intuitively know what your body needs to thrive. For some women, synthetic hormones work. For others, the side effects don’t outweigh the benefits, and natural hormone therapy is a better fit to rebalance hormones and gain a life of fulfillment and joy.

References:
  1. Journal of General Internal Medicine. March 7, 2007. “Bioidentical Hormones for Menopausal Hormone Therapy: Variation on a Theme.” http://link.springer.com/article/10.1007/s11606-007-0141-4/fulltext.html.
  1. National Institutes of Health. News Release. http://www.nhlbi.nih.gov/whi/pr_02-7-9.pdf.

NP’s & Practicing Alone: Minnesota Becomes 19th State

Nurse Practitioner State Practice Environment Map

Minnesota Becomes 19th State to Provide Patients with Full and Direct Access to Nurse Practitioner Services

AANP commends Governor Dayton and the Minnesota legislature on passage of Senate File 511 and urges other states to take similar steps to modernize licensure laws.

AUSTIN, TX (May 13, 2014) – Angela Golden and Kenneth Miller, Co-Presidents of the American Association of Nurse Practitioners (AANP), welcome the news that Minnesota’s Governor Dayton and the Minnesota legislature have passed Senate File 511, retiring the requirement that nurse practitioners maintain career-long collaborative agreements. The move makes Minnesota the 19th state, plus the District of Columbia, offering patients full and direct access to nurse practitioner services. According to AANP, it is an important step that improves access to care and more effectively uses nurse practitioners to meet the state’s growing health care needs.

Golden and Miller said: “Minnesota legislators overwhelmingly voiced their support for the evidence surrounding nurse practitioner quality and care. By signing Senate File 511 into law, they’ve removed a needless regulatory bottleneck that better positions the state to meet existing and future health care workforce needs. This step will quickly begin to positively impact the health of Minnesotans, and has the potential to reach underserved pockets of the state with new, flexible, coordinated care models.

“That said, Senate File 511 does include concessions to state medical associations – organizations that would have otherwise continued actively opposing the proposed law – that leave some health care challenges in place. This comes at a time when the changing demographics of health care, especially primary care, necessitates that states make full use of the nurse practitioner workforce. The nursing community is committed to addressing these challenges in future sessions to ensure that patients have a choice of health provider and receive full access to the health services they need.

“We urge lawmakers in all states to adopt the national standards for nurse practitioners recommended by the Institute of Medicine, the National Governors Association and the National Conference of State Legislatures, and adopt the consensus model from the National Council of State Boards of Nursing.”

Download State Regulatory Map Here

Resources
American Association of Nurse Practitioners – http://www.aanp.org/press-room/press-releases/161-press-room/2014-press-releases/1518-minnesota-becomes-19th-state-to-provide-patients-with-full-and-direct-access-to-nurse-practitioner-services

Breast Cancer & Common Myths

Overview: This article breaks through the common myths about HRT and breast cancer, and identifies the facts around this subject.

The Facts

One of the most common concerns raised by those interested in hormone replacement therapy is related to the perceived risk of breast cancer.

“Most experts in the medical field today would agree that hormones might influence breast cancer but do not cause breast cancer. Breast cancer originates in a mutation.” – Dr. Leon Speroff, MD, NCMP Professor Emeritus, OB/GYN, Oregon Health & Science University

World Health Organization: Women’s Health Initiative Study

In 2002, a study conducted by the Women’s Health Initiative on synthetic hormones was halted early due to reportedly perceived adverse and serious side effects (1). Doctors misunderstood the WHI findings. Many women who’ve had hysterectomies shared their fears and concerns about how their doctors put them on and then took them off of hormones despite the risks for osteoporosis, heart disease, and breast cancer.

In 2013, an article written by the Yale School of Medicine appeared in the American Journal of Public Health and was reported in Yale News (2). The widespread rejection of estrogen therapy after the 2002 Women’s Health Initiative (WHI) study has most likely led to almost 50,000 unnecessary deaths over the last 10 years among women aged 50 to 69 who have had a hysterectomy.

Prior to the incorrect reporting in 2002, the Yale authors estimated that 90 percent of women age 50 to 59 who had hysterectomies took estrogen to control hot flashes, prevent osteoporosis, and treat other diseases related to hormone deficiency. But, by 2013, approximately 10 percent of women aged 50 to 59 take estrogen therapy. The remaining 90 percent are putting their lives at risk over incorrect information about hormone replacement therapy and breast cancer.

The truth is that for women without a uterus, estrogen-only therapy may be life saving. Women who took estrogen had fewer deaths each year for 10 years and were less likely to develop breast cancer and heart disease than those who took placebo (3).

In conclusion, “Distortion of details can prove to be nothing less than lethal,” the Yale authors wrote. “The Women’s Health Initiative findings need to be presented so that the very important differences between the two treatment modalities are emphasized and the benefits for hysterectomized women aged 50-59 years are appreciated. This effort has clearly been inadequate to date.”

Sally’s Story of Renewed Energy

“I was on hormone medications for years due to a hysterectomy at an early age, but could still not get regulated. The last straw was when intimacy had pretty much come to a screeching halt and felt more like a chore (like doing dishes!). I stopped all hormone medications and started the [natural] hormone treatments, and – oh my gosh – the changes are beyond amazing. I have more energy, no more mood swings or hot flashes, I sleep at night, and my husband feels like he is trying to keep up with me for once.” – Sally S.

Resources
  1. National Institutes of Health, News Release. http://www.nhlbi.nih.gov/whi/pr_02-7-9.pdf.
  2. Yale News. July 18, 2013. http://news.yale.edu/2013/07/18/women-hysterectomies-estrogen-may-be-lifesaver-after-all.
  3. Yale News. July 18, 2013. http://news.yale.edu/2013/07/18/women-hysterectomies-estrogen-may-be-lifesaver-after-all.

Estrogen: A Lifesaver After All

Overview: This article describes hormone therapy in women with and without a uterus, and the true health risks associated with therapy.

Overview

The widespread rejection of estrogen therapy after the 2002 Women’s Health Initiative (WHI) study has most likely led to almost 50,000 unnecessary deaths over the last 10 years among women aged 50 to 69 who have had a hysterectomy, which Yale School of Medicine researchers revealed in a study published in the July 18 issue of the American Journal of Public Health.

Led by Dr. Philip Sarrel, emeritus professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences, and Psychiatry, the researchers analyzed United States census data, hysterectomy rates, and estimes of decline in hormone use in women aged 50 to 59 between 2002 and 2011.

Before 2002, it was standard practice for doctors to recommend estrogen therapy for this part of the population, and more than 90% of these women used it to treat symptoms such as hot flashes, and to prevent osteoporosis and other diseases related to menopausal hormone deficiency. Today, about 10% of these women use estrogen.

This sharp decline in estrogen usage was linked to results from one part of the large, federally funded WHI study in 2002. Women and their doctors became frightened of the dangers of post-menopausal hormones. But, according to Sarrel and his colleagues, this was a report about women with a uterus who took pills that combined estrogen and progestin. Women who have a uterus must take a second hormone (a progestin) to avoid a risk of uterine cancer. However, these results did not apply to women with no uterus who use estrogen-only therapy.

“Sadly, the media, women, and healthcare providers did not appreciate the difference between the two kinds of hormone therapy,” Sarrel said. “As a result, the use of all forms of FDA approved menopausal hormone therapy declined precipitously.”

Sarrel added that for women taking combined hormone therapy (at least the particular drug, Prempro, used in the WHI study), it was probably a good decision to avoid it because the WHI study showed a significant increase in breast cancer, heart disease, stroke, and blood clots to women who used this drug compared to placebo. However, for the women taking estrogen-only therapy, avoiding treatment does not appear to have been a good decision.

Results from the second part of the WHI study, which followed women who had no uterus and who took either estrogen-only or placebo were very different. A series of papers published by the WHI between 2004 and 2012 showed that estrogen-only therapy had mostly positive health outcomes. For example, in 2011 and 2012 the WHI reported that women who received estrogen compared to those who received placebo had fewer deaths each year for 10 years and were less likely to develop breast cancer and heart disease. For each of the 10 years the death rate among those not taking estrogen was 13 more per 10,000. Most of these women died from heart disease, while breast cancer accounted for almost all the other deaths.

Estrogen avoidance has resulted in a real cost in women’s lives every year for the last 10 years – and the deaths continue,” said Sarrel. “We hope this article will stir an overdue debate and raise consciousness about the health benefits of estrogen-only therapy for women in their 50s with no uterus.”

Other authors on the study are Dr. Valentine Y. Njike, Dr. Valentina Vinante, and Dr. David L. Katz. Sarrel is a consultant with Noven Therapeutics.

Citation
American Journal of Public Health
References
Yale News. For women with hysterectomies, estrogen may be a lifesaver after all. http://news.yale.edu/2013/07/18/women-hysterectomies-estrogen-may-be-lifesaver-after-all.

Estradiol and Hot Flushes

Overview: This article describes a study done to research the effect of the estradiol hormone on hot flushes

Abstract Objective

To assess the efficacy and safety of 17-beta estradiol buccal tablets in reducing hot flush frequency (HFF) in postmenopausal women.

Methods

Estradiol buccal tablets containing 0.05, 0.1, 0.2, or 0.4 mg or placebo were administered for 28 days to 99 postmenopausal women in a randomized, double-blind study, and 19 premenopausal women were studied concurrently for comparison of laboratory data. Objective and subjective assessments of HFF were obtained along with measures of estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH).

Results

Measurements of HFF revealed significant decreases from baseline in all estradiol groups (P < 0.01). All estradiol doses produced similar improvements in the vaginal maturation index. Mean serum estradiol levels increased as doses increased, but were lower than in the premenopausal subjects. Mean serum FSH and LH levels decreased in all estradiol groups but not to the levels of the premenopausal subjects. The greatest decrease occurred at the two highest estradiol doses.

Conclusion

A numerical dose-response relationship with hot flushes was seen in this pilot study comparing 0.05, 0.1, 0.2, and 0.4 mg buccal estradiol. Only 0.4 mg 17-beta estradiol significantly reduced the occurrence of hot flushes compared to placebo.

References
National Center for Biotechnology Information (NCBI). http://www.ncbi.nlm.nih.gov/pubmed/15474758.

Hysterectomies: Estrogen Avoidance, Effects & Death

Overview: An analysis of excess deaths among women with hysterectomies aged 50 to 59 years, this study examined the effect of estrogen avoidance on mortality rates.

Abstract Objectives

The effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59 years was examined.

Methods

A formula was derived to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the Women’s Health Initiative randomized controlled trial to the entire population of comparable women in the United States, incorporating the decline in estrogen use observed between 2002 and 2011.

Results

Over a span of 10 years, starting in 2002, a minimum of 18,601 and as many as 91,610 postmenopausal women died prematurely because of the avoidance of estrogen therapy (ET).

Conclusions

ET in younger postmenopausal women is associated with a decisive reduction in all-cause mortality, but estrogen use in this population is low and continuing to fall. The data indicates an associated annual mortality toll in the thousands of women aged 50 to 59 years. Informed discussion between these women and their healthcare providers about the effects of ET is a matter of considerable urgency.

Citation
American Journal of Public Health. http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2013.301295.
References
American Public Health Association. The mortality toll of estrogen avoidance. http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2013.301295.

Your Heart and Hormone Therapy

Overview: This article describes hormone therapy and heart disease risks.

Are you taking – or considering – hormone therapy to treat bothersome menopausal symptoms?

Understand the potential risks to your heart and whether or not hormone therapy is right for you.

Overview

Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal women to relieve hot flashes and other menopause symptoms. Hormone replacement therapy was also thought to reduce the risk of heart disease.

Before menopause, women have a lower risk of heart disease than men do. But, as women age and their estrogen levels decline after menopause, their risk of heart disease increases. In the 1980s and 1990s, experts advised older women to take estrogen and other hormones to keep their hearts healthy.

However, hormone replacement therapy (also called menopausal hormone therapy), has had mixed results. Many of the hoped-for benefits failed to materialize for large numbers in women. The largest randomized, controlled trial to date actually found a small increase in heart disease in postmenopausal women using combined (both estrogen and progestin) hormone therapy. For women in this study using estrogen alone, there was no increased risk in heart disease.

Other studies suggest that hormone therapy, especially estrogen alone, may not affect – or may even decrease – the risk of heart disease when taken early in postmenopausal years. However, these studies can be confusing to interpret into practice, since study outcomes can be affected by many factors, such as the ages of the study participants, the time elapsed since menopause, and the duration of the hormone therapy use. Continued research will help doctors more clearly understand the relationship between menopausal hormone therapy and heart disease.

Risks in Perspective

If you are having a tough time with symptoms of menopause but worry about how hormone therapy will affect your heart, talk with your healthcare provider to put your personal risk into perspective. Consider these points:

  • The risk of heart disease to an individual women taking hormone therapy is very low. If you are in early menopause, have moderate to sever hot flashes and other menopausal symptoms, and are otherwise healthy, the benefits of hormone therapy likely outweigh any potential risks of heart disease.
  • Your individual risk of developing heart disease depends on many factors including family medical history, personal medical history, and lifestyle practices. Talk to your doctor about your personal risks. If you are at low risk of heart disease, and your menopausal symptoms are significant, hormone therapy is a reasonable consideration.
  • Risk differs for women with premature menopause or premature ovarian failure. If you stopped having periods before age 40 (premature menopause) or lost normal function of your ovaries before age 40 (premature ovarian failure), you have a different set of heart and blood vessel (cardiovascular) health risks compared with women who reach menopause near the average age of about 50. This includes a higher risk of coronary heart disease. If you have premature ovarian failure, you’ll likely be given hormone therapy to protect against heart disease.

Menopausal hormone therapy risks may vary depending on:

  • Whether estrogen is given alone or with a progestin
  • Your current age and age at menopause
  • The dose, type of estrogen and route, or how you take it (oral, transdermal, transvaginal)
  • Other health risks, such as your family medical history and cancer risks

Who Should Not Take Hormone Therapy

If you’ve already had a heart attack, menopausal hormone therapy is not for you.

If you already have heart disease or you have a history of blood clots, the risks of hormone therapy have been clearly shown to outweigh any potential benefits.

How to Limit the Risks

Talk with your healthcare provider  about these strategies to reduce the risks of menopausal hormone therapy:

  • Try a form of hormone therapy that has limited systemic effects. Estrogen and progestin are available in many forms including pills, skin patches, gels, vaginal creams, and slow-releasing suppositories or rings that you place in your vagina. Low-dose vaginal preparations of estrogen – which come in cream, tablet, or ring form – can effectively treat vaginal symptoms while minimizing absorption into the body. Similarly, hormones delivered through skin patches aren’t as extensively metabolized in the body and have less potential for unwanted side effects.
  • Minimize the amount of medication you take. Use the lowest effective dose for the shortest amount of time needed to treat symptoms, unless you’re younger than age 45. In that case, you need enough estrogen for protection against long-term health effects of estrogen deficiency. If you have lasting menopausal symptoms that significantly impair your quality of life, your doctor may recommend longer term treatment.
  • Make healthy lifestyle choices. Counter the risks of developing heart disease by making heart-healthy lifestyle choices. Don’t smoke or use tobacco products. Get regular physical activity. Eat a healthy diet focusing on fruits, vegetables, whole grains, and low-fat protein. Maintain a healthy weight. Get regular health screenings to check your blood pressure and cholesterol levels to detect early signs of heart disease.
  • Seek regular follow-up care. See your healthcare provider regularly to ensure that the benefits of hormone therapy continue to outweigh the risks, and for cancer screenings such as mammograms and pelvic exams.

A Balancing Act

Women of all ages should take heart disease seriously. Among women in the United States, nearly one in three deaths each year is due to heart and blood vessel (cardiovascular) disease.

Most healthy women who are within five years of menopause can safely take short-term hormone therapy for menopausal symptoms without significantly increasing the risk of heart disease.

If you experience classic menopausal symptoms including intolerable hot flashes, vaginal dryness, or insomnia, talk to your healthcare provider about how you can relieve troublesome symptoms without putting your health at risk.

References
Mayo Clinic. Hormone Replacement Therapy and Your Heart. http://www.mayoclinic.org/diseases-conditions/menopause/in-depth/hormone-replacement-therapy/art-20047550

Your Brain & HRT

Overview: While different studies are conflicting, some observational data suggest that hormone replacement therapy (HRT) may reduce the risk of cognitive decline and dementia. This article outlines some key statistics around the topic.

Objective

The objective of this article is to review and evaluate studies of HRT for preventing cognitive decline and dementia in healthy postmenopausal women.

Data Sources

Data was gathered from the following sources:

  • Studies within English-language abstracts in MEDLINE (1966-August 2000), HealthSTAR (1975-August 2000), PhyschINFO (1984-August 2000)
  • Cochrane Library databases
  • Additional articles listed in resources

Study Selection

Randomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline. Additionally, cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were identified.

Data Extraction

29 studies met inclusion criteria and were rated. Two reviewers rated study quality independently and 100% agreement was reached on Jadad scores, and 80% agreement was reached on U.S. Preventative Services Task Force quality scores. A final score was reached through consensus if reviewers disagreed.

Data Synthesis

Studies of cognition were not combined quantitatively because of heterogeneous study design. Women symptomatic from menopause had improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions. Generally, no benefits were observed in asymptomatic women.

A meta-analysis of observational studies suggested that HRT was associated with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence interval, 0.53-0.82). However, possible biases and lack of control for potential confounders limit interpretation of these studies.

Studies did not contain enough information to assess adequately the effects of progestin use, various estrogen preparations or doses, or duration of therapy.

Conclusions

In women with menopausal symptoms, HRT may have specific cognitive effects, and future studies should target these effects. The meta-analysis found a decreased risk of dementia in HRT users, but most studies had important methodological limitations.

Resources
The Journal of the American Medical Association (JAMA). http://jama.jamanetwork.com/article.aspx?articleid=193670.

Estradiol and Bone Loss

Overview: This article describes a study done to research the effect of the estradiol hormone on bone loss that commonly occurs post-menopause.

Abstract

The effect of percutaneous estradiol alone and combined with natural progesterone on postmenopausal bone loss was studied. A total of 57 women who had experienced a natural menopause six months to three years previously entered the study. After an initial examination, the women were allocated in a blinded pattern to treatment with either three milligrams of percutaneous estradiol or placebo.

The code was broken after one year of treatment, and the women receiving estradiol continued with a cyclic addition of progesterone, whereas those receiving placebo continued with placebo. The women were examined every three months during the two years of treatment. Measurement of the bone mineral content in the forearms (single photon absorptiometry), and the spine and total skeleton (dual photon absorptiometry) showed a significant decrease of five to seven percent in the placebo group during the two years of treatment, whereas it remained constant in all bone compartments in the estradiol group. Addition of progesterone did not influence the results.

Biochemical estimates of calcium metabolism changed toward a premenopausal level in the estradiol group, but remained unchanged in the placebo group. We conclude that percutaneous estradiol is effective as preventive therapy and postmenopausal bone loss, and that addition of progesterone does not influence bone or calcium metabolism.

References
National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/pubmed/3541622.

Testosterone and Heart Disease

Overview: This article outlines how testosterone may work to reduce Cardiometabolic Disease.

The Research

Research from Boston University of Medicine (BUSM) suggests that testosterone treatment in hypogonadal (testosterone deficient) men restores normal lipid profiles, and may reduce the risk of cardiovascular disease. These findings currently appear online in the International Journal of Clinical Practice.

Metabolic Syndrome (MetS) is associated with an increased risk for cardiovascular disease and diabetes mellitus. There is a strong association between MetS and testosterone deficiency. Hypogonadal men are more likely to suffer from metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and hypertension. Additionally, obese and overweight men also may exhibit testosterone deficiency.

In this observational study, BUSM researchers investigated the effects of testosterone treatment in 255 hypogonadal men between the ages of 33-69 and observed them for five years. They found that men treated with testosterone therapy experienced a gradual reduction of their total cholesterol, low density lipoprotein cholesterol (LDL or bad cholesterol), triglycerides, and increased high density lipoprotein (HDL or good cholesterol).

“In addition to improving their cholesterol levels, we found that the testosterone treatment resulted in marked reductions in systolic and diastolic blood pressure as well, suggesting amelioration of hypertension,” explained lead author Abdulmaged M. Traish, MBA, Ph.D., Professor of Biochemistry and Urology, as well as Research Director of the Institute of Sexual Medicine at BUSM.

Traish found this treatment also reduced fasting blood glucose and hemoglobin A1c, a surrogate marker of hyperglycemia, suggesting that testosterone treatment may improve insulin sensitivity and hyperglycemic control. It also reduced the levels of inflammatory biomarkers such as C-reactive protein (CRP) and markers of liver dysfunction such as alanine aminotransferase and aspartate aminotransferase, suggesting reduction in the inflammation responses.

“These data are congruent with our previous work in which we reported that long-term testosterone resulted in a gradual decline in weight and waist circumference and strongly suggests that testosterone therapy in hypogonadal men may prove useful in reducing the risk of cardiometabolic diseases,” Traish added.

Summary

Testosterone may help to reduce symptoms of weight gain, high blood sugar, increased urination, fatigue, and blurred vision in men.

Resources
Boston University Medical Center. October 23, 2013. “Testosterone therapy may reduce risk of cardiovascular disease.” ScienceDaily. https://www.sciencedaily.com/releases/2013/10/131023112636.htm.

Testosterone in Women

Overview: This article outlines the results of studies done of testosterone therapy in women.

Abstract

Female sexual desire appears to be partially dependent on the androgen hormone, which has led to the use of testosterone in women for low libido (sexual drive). Despite this benefit, the long-term safety of testosterone as a hormone replacement or therapy has not been well established. Side effects of testosterone therapy include mild and reversible acne and hirsuitism (unwanted male-pattern hair growth), as well as changes to the lipid profile with oral, but not transdermal testosterone. Short-term studies that lasted two years or less showed that for serum plasma testosterone levels at the upper portion or slightly above the reference range for reproductive-aged women, testosterone does not increase the risk of hepatotoxicity, endometrial hyperplasia, or behavioral hostility.

No adverse cardiovascular effects, including changes in blood pressure, blood viscosity, arterial vascular reactivity, hypercoagulable states, and polycythemia have been shown. Data is mixed with outcomes of breast cancer risk, with some experimental studies suggesting a decrease in estrogen-induced breast epithelial proliferation with lose dose testosterone. Additionally, models of superphysiologic testosterone levels, such as polycystic ovarian disease, have not shown an increased risk of breast cancer.

As with all hormone therapy in postmenopausal women, testosterone therapy should be individualized and requires that each woman weight the risk and benefits. Nevertheless, only long-term safety studies will provide conclusive evidence as to testosterone safety in women.

References
The European Menopause Journal (Maturitas). http://www.maturitas.org/article/S0378-5122%2809%2900037-1/abstract.

Facts About Women and Heart Disease

Statistics

Below are statistics around women and heart disease:

  • Heart disease is the leading cause of death for women in the United states, killing 292,188 women in 2009. That’s 1 in every 4 female deaths (1).
  • Although heart disease is sometimes thought of as a “man’s disease,” around the same number of women and men die each year of heart disease in the United States. Despite increases in awareness over the past decade, only 54% of women recognize that heart disease is their number one killer (2).
  • Heart disease is the leading cause of death for African American and Caucasian women in the United States. Among Hispanic women, heart disease and cancer cause roughly the same number of deaths each year. For Native American or Alaska Native as well as Asian or Pacific Islander women, heart disease is second only to cancer (3).
  • About 5.8% of all Caucasian women, 7.6% of African American women, and 5.6% of Mexican American women have coronary heart disease (5).
  • 64% of women who die suddenly of coronary heart disease have no previous symptoms (4). Even if you have no symptoms, you may still be at risk for heart disease.

Symptoms

While some women have no symptoms, others experience:

  • Angina (dull, heavy to sharp chest pain or discomfort)
  • Pain in the neck, jaw, or throat
  • Pain in the upper abdomen or back

These symptoms may occur during rest, at the beginning of physical activity, or can be triggered by mental stress (6).

Women are more likely to describe chest pain that is sharp and burning, and more frequently have pain in the neck, jaw, throat, abdomen or back (6).

Sometimes heart disease may be silent and not diagnosed until a woman experiences signs or symptoms of a heart attack, heart failure, an arrhythmia (6), or stroke.

These symptoms include:

  • Heart Attack – Chest pain or discomfort, upper back pain, indigestion, heartburn, nausea/vomiting, extreme fatigue, upper body discomfort, and shortness of breath.
  • Arrhythmia – Fluttering feelings in the chest (palpitations) (6).
  • Heart Failure – Shortness of breath, fatigue, and swelling of the feet, ankles, legs, and abdomen.
  • Stroke – Sudden weakness, paralysis (inability to move), or numbness of the face, arms and legs, especially on one side of the body. Other symptoms may include confusion, trouble speaking or understanding speech, difficulty seeing in one or both eyes, shortness of breath, dizziness, loss of balance or coordination, loss of consciousness, or a sudden and sever headache (7).

Risk Factors

Key risk factors for heart disease include high blood pressure, high LDL cholesterol, and smoking. About half of Americans(49%) have at least one of these three risk factors (5).

Several other medical conditions and lifestyle choices can also put people at a higher risk for heart disease, including:

  • Diabetes
  • Overweight and obesity
  • Poor diet
  • Physical inactivity
  • Excessive alcohol use

Screening

To reduce your chances of getting heart disease, it’s important to (8):

  • Know your blood pressure. Having uncontrolled blood pressure can result in heart disease. High blood pressure has no symptoms, so it’s important to have your blood pressure checked regularly.
  • Talk to your healthcare provider about whether you should be tested for diabetes. Having uncontrolled diabetes raises your chances of heart disease.
  • Make healthy food choices. Being overweight and obese raises your risk of heart disease.
  • Limit alcohol intake. You should limit your intake to one drink per day or less.
  • Lower your stress level. Find healthy ways to cope with stress.
CDC’s Public Health Efforts Related to Heart Disease
Additional Information
For more information on women and heart disease, visit the following Web sites:
Resources
Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC. Deaths: final data for 2009 [PDF-2M].National vital statistics reports. 2011;60(3).
Mosca L, Mochari-Greenberger H, Dolor RJ, Newby LK, Robb KJ. Twelve-year follow-up of American women’s awareness of cardiovascular disease risk and barriers to heart health. Circulation: Cardiovascular Quality Outcomes. 2010;3:120-7.
Heron M. Deaths: Leading causes for 2008 [PDF-2.7M]National vital statistics reports. 2012;60(6).
Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart AssociationCirculation. 2012;125(1): e2–220.
CDC. Million Hearts: strategies to reduce the prevalence of leading cardiovascular disease risk factors. United States, 2011. MMWR2011;60(36):1248–51.
National Heart, Lung and Blood Institute. What Are the Signs and Symptoms of Heart Disease? [cited 2013 July 19, 2013]. www.nhlbi.nih.gov/health/health-topics/hdw/signs.html.
National Heart Lung and Blood Institute. What are the Signs and Symptoms of a Stroke? [cited 2013 July 19, 2013]. www.nhlbi.nih.gov/health/health-topics/topics/stroke/signs.html.
U.S. Department of Health and Human Services, Office on Women’s Health. Heart Disease: Frequently Asked Questions. 2009. [cited 2013 July 19, 2013]. http://www.womenshealth.gov/publications/our-publications/fact-sheet/heart-disease.pdf [PDF-1.7M].
Center for Disease Control and Prevention. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_women_heart.htm.

What to Expect (with Natural Hormone Replacement Therapy)

Natural hormones (or Bio-Identical) when seen under a microscope in a lab look the same as hormones made by your body. (and yes, your body does see them exactly just like the ones it makes on its own!)

Natural hormones are made at a compounding pharmacy which produces pellets that are custom made to a specific dosage or range for that type of hormone. The pellets are typically the size of a grain or rice…sometimes even smaller! (Example would be a 50 mg Testosterone pellet, or a 3 mg Estrogen pellet.)  

Re-balancing your hormones with natural hormone therapy takes time. Usually we say it takes 3 months (3 months = 1 cycle or 90 days) until you are feeling better. Sometimes it takes more than one cycle to get you back to feeling your best.

You come in for a lab visit and your hormones are tested periodically over the course of your cycle. You’ll have a regular symptom tracker that shows your progress (just like you’d use a  food diary to track how you feel after you eat.) Our staff listens to your feedback  so you can get the best results. We want you to feel better!

Keep in mind during your cycle, it’s possible your hormones might still be out of balance and may cause side effects. (Sometimes, they seem just like the symptoms you’re trying to get relief** from.)

Trust me, we’ve all been there, done that before. And always remember – we are here for you every step of the way. It’s your health, your choice, your journey…

References:
The Truth About Hormone Therapy (Wall Street Journal) https://www.wsj.com/articles/SB123717056802137143
**No testimonial on this website is intended nor should be construed as medical advice or diagnosis. While these results are typical, your individual results may vary.  Information presented is offered for educational and informational purposes only, and should not be construed as personal medical advice. If you choose to use any information given here, you should consult with your personal provider regarding your own medical care.

6,000 women enter menopause every day

A symphony orchestra is made up of many instruments that when put together correctly makes beautiful music. Just like in our bodies, for us to feel, act and look our best, our hormonal system must function and work together in balance. Human hormones are designed to work together. And if one is altered or deficient, it will affect the actions of all the other hormones.

It’s estimated that 3,500 to 6,000 women enter menopause every day in the United States.  Menopause occurs when a woman has had no natural menstrual cycle for 12 months. Menopause can be the best time in a woman’s life.  Most no longer have to worry about pregnancy and we’re usually young enough to still be sexually interested.

Menopause is a time when women get the opportunity to work on themselves, since we have been busy taking care of other people.
Most people will agree that in general women are staying at lot healthier and the new “middle age now begins at 60.”

However, if our “hormonal symphony” is out of tune, we can begin having symptoms 2-20 years ahead of time. This time in our life is called peri-menopause. A woman may still have cycles during this time, but they may become more irregular, bleeding changes, symptoms can be present and unpredictable and changes our quality of life.

Everybody’s body is unique and the symptoms of both peri-menopause and menopause can be similar. While some may experience no symptoms and sail right through, others may have symptoms so severe that it disrupts the quality of life and puts their careers, relationships and even their health at risk.

Some common symptoms include: hot flashes/night sweats, weird dreams, snoring and sore breasts, all the changes that happen “down there” like urinary tract infections, have to pee often and leak a little when you laugh, cry or move, vaginal dryness, itching and odor. Then there are the heart palpitations and rapid pulse, headaches, lower back pain and achy joints on top of unwanted varicose veins. Digestion issues like bloating, weight gain, feeling fat, indigestion and flatulence can make one lose their sexy and desire for intimacy. With the loss of sexual interest some experience painful intercourse due to vaginal dryness. If that’s not enough, some women will experience insomnia or other sleep disturbances, mood swings, irritability, depression, panic attacks or anxiety, dizzy spells, lack of focus or concentration and short term memory loss. What about dry skin or feeling like your skin is crawling with bugs so you itch all over? And finally the hair we’re losing on the top of our head seems to appear in other unwanted places like face and chin.

The “normal age” to go through menopause ranges from 35 to 55 years making it easily one half of our life without a menstrual cycle.

Until the last twenty years or so, the only available hormonal therapy in many countries has been synthetic hormone replacement like the birth control pill or IUD, patches, etc.   Synthetic hormones are replacement hormones that do not have the same chemical structure we are born with.

For some, synthetic hormones work just fine and pose no risk. For others, this is not the case.

Natural hormone replacement therapy means using plant based hormones that are biologically identical to what the body should be making but isn’t or can’t. When viewed under the microscope, these hormones have the same molecular or chemical structure as the human hormones the body made before menopause.

The one size fits all approach doesn’t work. Each woman is unique and needs a customized and individualized approach. Natural hormonal therapy is the best way to replace hormones safely and studies have shown that women who use hormone replacement live longer than those who do not.

Remember each person’s hormonal response is unique as their fingerprints. How we may respond to hormone replacement therapy is related to our genetic profile, stress level, health condition – do we still have our ovaries or uterus, environment, nutritional supplementation, and what we eat.

Hormone replacement should be considered with a thorough understanding of how all of the human body’s hormones work with each other.

The science of today’s medicine is changing from the previous thought process of crisis disease management – where one agent caused a single disease that could be treated with one medication – to a new shift in understanding that human beings are complex and a wholistic approach restores balance and improves health and longevity.

References:
Endocrinology – A Woman’s Hormonal Symphony: Hormone Replacement Therapy by Pamela Wartian Smith, M.D., MPH, MS; Director, Center for Healthy Living and Longevity, Traverse City, MI USA; Director, The Fellowship in Metabolic, Anti-Aging and Functional Medicine.
Information presented is offered for educational and informational purposes only, and should not be construed as personal medical advice. If you choose to use any information given here, you should consult with your personal provider regarding your own medical care.

Hot Flashes and Menopause

As we age, everyone begins to experience a decrease in natural hormone levels. This is normal.
However, when the decrease turns into a deficiency of Estrogen, Progesterone, and Testosterone in women and Testosterone in men, this may cause a bunch of symptoms that affect your health, well-being and quality of life.

The Change?

Hot flashes (flushes) are often seen in women “going through the change.”  There may also be a significant number of other changes in a woman’s body at this time such as trouble sleeping, low sex drive, mood swings, irritability, crying for no logical reason, fatigue, skin and hair.  And did you know that some men may experience similar symptoms as they enter “andropause,” often described as the male counterpart to female menopause?

Hot flashes are some of the most troublesome symptoms of menopause and andropause.  They often occur suddenly and for no apparent reason. The person describes feeling like the room is very hot and you might even hear them say, “is it hot in here or is it just me?” then sweat breaks out especially on the face and chest, and the skin turns red including their ears.  All this happens because of quick vasodilatation or blood vessels opening wider near the surface of the skin and gives off more heat. Quickly declining hormone levels can start this response.

For women, the two ovaries normally produce the majority of testosterone and estradiol and it’s often thought the uterus produces progesterone.  Bodies are born with the ability to produce hormones unless there is a genetic anomaly.   Increased production starts at puberty and continues through menopause – when the “menses paused.” Meaning our period has stopped for good.  From the onset of the first period, most medical professionals believe that each woman only has a certain number of eggs. When the last of these eggs in the basket (ovaries) is gone, the ovaries dramatically decrease or even stop the production of these hormones.

Testosterone Loss – Many believe the first hormone to begin declining in women is testosterone, usually by age 30. Less energy, decreased sex drive, weight gain and mood changes can result.  By age 35 a woman begins to produce less progesterone which may make it harder to get pregnant.  Lack of or low progesterone can cause heavy periods, cramps, water retention, breast tenderness, uterine fibroids, fibrocystic breast disease or lumpy boobs as some have described, anxiety, poor sleep and irregular periods.

Finally, estradiol begins to decline more quickly and then hot flashes, night sweats, hair loss or changes, painful sex, vaginal dryness along with dry, thin skin and the feeling of “I just don’t feel like myself anymore” or “I’ve lost my sexy and I want it back!”

How can women avoid the symptoms of menopause?

The truth is some can’t!  There is no way around it naturally if a woman has had her ovaries and uterus removed.  Unfortunately, many women suffer needlessly with embarrassing symptoms like hot flashes and/or night sweats, irritability, sudden tears, memory lapses and incontinence.  Yikes! Many seeking relief discover that trying to find a satisfactory solution mysterious and often wonder why can’t my doctor help me?

We’ve often hear women say, “Before starting natural hormone therapy I was experiencing at least 15-20 hot flashes a day” or “I’m right in the middle of a meeting and then it starts….”  Desperately tries synthetic hormones but gets very little relief so she’s referred to MEDSTUDIO.  And after starting therapy she reports, “Now I have no more hot flashes, sleeping great, lots of energy and my husband is happier too.” While each patient reacts differently to the treatments, it is not unusual for our patients to experience substantial relief from symptoms very quickly, especially hot flashes.

Our natural hormone therapy program is designed for monitoring of hormone levels over the course of treatment so that each person’s desired hormonal levels can be reached at a pace that is comfortable for them.

Interested in learning more?

Women and even men should not have to suffer in silence. If you have symptoms and want relief, contact someone at MedStudio to find out more. And of course, information is great when evaluating and learning about your health choices. Ultimately, only a qualified licensed medical provider can make a qualified diagnosis and recommendation.   While this document is not to be used to diagnose, treat or cure any type of illness or health condition, we hope it will make you interested enough to seek more information and get your life back. After all, it’s Your Health. Your Choice. Your Journey.  We are here to guide you.

Lack of Intimacy & Estrogen Levels

Never give up…

Fear, dread, avoidance, lack of confidence, sense of loss, relational tension, anxiety about the future, hopeless resignation. Do any of these describe your inner struggle with painful intercourse?  Have you given up on creams, gels, and lubricants because they just don’t seem to help enough? Do you long to be the carefree, spontaneous person you once were before age or a hysterectomy began to take a toll? For women who lack enough estradiol or estrogen to maintain adequate moisture in the vagina, once pleasurable intercourse may be gone.

A woman’s ovaries usually produce the hormones estradiol, progesterone, and testosterone.  Blood levels of estradiol vary from day to day throughout the menstrual cycle starting low just after menstruation, then rising sharply within the first 8 to 10 days of the cycle. This is followed by a period when estradiol declines somewhat, followed by another surge of estradiol. This may explain mood swings and fluid retention varying from time to time.

So What’s Missing?

Estrogen is very important in keeping the tissues of the vagina lubricated and healthy.1 Normally, the lining of the vagina creates a clear, lubricating fluid. Estradiol is responsible for the vagina to be easily stimulated to produce moisture any time during the female cycle, providing for ease of intercourse. Yet estradiol levels start to decline in menopause, usually between 40 – 50 for most women.

A condition called atrophic vaginitis can develop by decreased estrogen. Without sufficient estradiol, the mucosa of the vagina becomes dry and feels as if it is cracking. Itching, or burning on urination may also occur. During intercourse chafing is inevitable, making intercourse painful and unbearable. Not only is estradiol necessary for maintaining vaginal moisture, but it also performs over four hundred vital functions in a female. Vaginal dryness can also lead to other health concerns such as: Yeast or bacterial infections of the vagina, sores or cracks in the walls of the vagina, and cause pain or bleeding in intercourse.

Solution: Natural Hormone Therapy  

Replacement of lost estradiol with natural estradiol through natural hormone therapy restores the body’s own lubrication as opposed to simply providing a covering for stressed tissue with creams and gels. These topical preparations then could be viewed as supplementation to systemic renewal gained replaced estrogen in the system.

Interested in learning more?

Women and even men should not have to suffer in silence. If you have symptoms and want relief, contact someone at MedStudio to find out more. And of course, information is great when evaluating and learning about your health choices. Ultimately, only a qualified licensed medical provider can make a qualified diagnosis and recommendation.

While this document is not to be used to diagnose, treat or cure any type of illness or health condition, we hope it will make you interested enough to seek more information and get your life back.

After all, it’s Your Health. Your Choice. Your Journey.

We are here to guide you through menopause.

1                    http://www.nlm.nih.gov/medlineplus/ency/article/000892.htm

The role of oxidative stress in menopause

The role of oxidative stress in menopause

Sejal B. Doshi and Ashok Agarwal

Abstract

This review will discuss the concept of reproductive aging, which includes the definition of menopause, its symptoms, and predisposing conditions. It will elaborate upon the contributory factors implicated in the pathogenesis of menopause, focusing most prominently on oxidative stress. Specifically, this paper will explain how oxidative stress, in the form of free radicals and antioxidant deficiencies, has been directly linked to the decline of estrogen during reproductive aging. Additionally, this paper will elaborate upon the treatment options aimed at mitigating the menopausal symptoms and hormonal deficiencies that can lead to various disease processes. Treatment options such as hormonal therapy, antioxidant supplementation, and lifestyle modification have been explored for their effectiveness in treating and preventing the symptoms and sequelae of menopause. The majority of information in this review was obtained through PubMed and the National Library of Medicine. While most references in this paper are original research articles, a limited number of references are comprehensive reviews on the topic.

Keywords: Antioxidants, cardiovascular disease, catalase, estrogen, hormonal therapy, hot flashes, malonaldehyde, menopause, osteoporosis, oxidative stress, phytoestrogens, reproductive aging, superoxide dismutase, Vitamin A, Vitamin C, Vitamin E

INTRODUCTION

Menopause, a form of reproductive aging, is defined as the permanent cessation of ovarian follicular activity and eventually, the menstrual cycle.[1,2] Normally, menopause is a natural process of the body; however, it can be the result of other causes such as surgery, chemotherapy, or iatrogenic insult.[1] Additionally, two hormones (progesterone and estrogen) integral to reproductive aging are no longer produced during menopause.[3,4,5] Specifically, the decline and eventual cessation of estrogen production has been shown to cause a variety of symptoms during menopause, affecting each woman differently. These include hot flashes, night sweats, breast tenderness, vaginal dryness, irregular menses, mood changes, vaginal atrophy, osteoporosis, heart disease, and sometimes premature ovarian failure.[6] Many therapies have targeted this hormonal decline in estrogen and have also expanded to include lifestyle modifications, such as diet and exercise.[7] Additionally, foods rich in antioxidants have been shown to be of great benefit in women experiencing menopausal symptoms because they help to eliminate oxidative stress within the body. Overall, this paper will discuss in great detail the stress of free radicals and antioxidant deficiencies, both of which play a role in the pathogenesis of menopause.[3]

METHODS

The majority of information in this review was obtained through English-only articles from the PubMed and National Library of Medicine databases. Only literature containing up-to-date and relevant information on the topic was selected, starting from 1988 to 2013. Specifically, the following key terms were used to generate the literature search for this review paper: Menopause, oxidative stress, antioxidants, estrogen, free radicals, herbal antioxidants, pharmacotherapy, hormonal therapy, phytoestrogens, osteoporosis, cardiovascular disease, and vasomotor disturbances. While most references in this paper are original research articles, a limited number of references are comprehensive reviews on the topic.

HORMONAL AND CHEMICAL IMBALANCES OF MENOPAUSE

Menopause is a gradual process that occurs over a period of years in females who are typically between 45–55 years of age. It marks the beginning of a woman’s age-related fertility decline via a decrease in the number of ovarian follicles produced.[2] This change in reproductive potential is the direct result of a decline in production of hormones by the ovaries, which causes physical manifestations that negatively impact the quality of life of menopausal women.[3] In regards to the hormonal changes that occur, the earliest involves a rise in follicle stimulating hormone (FSH) followed years later by a rise in luteinizing hormone (LH).[4] Studies have attributed this rise in FSH during menopause to a decreased production of inhibin B, a dimeric glycoprotein that suppresses FSH.[8] Specifically, this compound was found to decline during both the follicular and luteal phases of the menstrual cycle, causing a rise in the FSH levels, and is therefore considered an early indicator of reproductive aging.[3] Overall, these hormonal imbalances resulting from the permanent cessation of ovarian function contribute to significant changes in the menstrual bleeding patterns during the perimenopausal period.[6]

In addition to changes in FSH and LH levels, there is a substantial decrease in the amount of estrogen produced during menopause. Acting as a lipophilic hormone, estrogen normally helps to promote female secondary sexual characteristics, such as breast development and female patterned hair growth. It not only plays a pertinent role in the female reproductive system, but also induces a variety of beneficial effects in other areas of the body.[9] Specifically, this hormone increases hepatic production of binding proteins like sex hormone binding globulin, maintains appropriate fluid balance in the body by allowing for salt and water retention, promotes coagulation, and it allows for a favorable lipid profile via increases in high density lipoprotein (HDL) and decreases in low density lipoprotein (LDL).[9,10]

Estrogen’s release is mediated by FSH produced from the anterior pituitary gland, which in turn stimulates the granulosa cells of the ovary to synthesize estrogen. Specifically, in the ovary, estrogen is produced from the conversion of androgens via the enzyme aromatase[11] [Figure 1]. Moreover, estrogen is synthesized in three forms: Estradiol, estriol, and estrone.[12] Specifically, 17β-estradiol is the most common and potent form of estrogen predominating during the premenopausal and perimenopausal periods; whereas estrone, the much weaker form, is prevalent during the postmenopausal phase. The latter form of estrogen is normally produced from the conversion of androstenedione in adipose tissue and the liver.[13] In addition to being produced in the ovaries and a portion of the ovary known as the corpus luteum, estrogens are synthesized in smaller amounts by other tissues, such as adrenal glands, fat cells, breast tissue, and hepatocytes.[12]

Figure 1

Two cell theory of estrogen production: Luteinizing hormone stimulates the production of androstenedione from cholesterol in the theca cells. This androgen is then transported to the granulosa cells, where it is converted to estrone. Follicle stimulating 

Another reproductive hormone that declines significantly during menopause is progesterone. Also lipophilic in nature, progesterone promotes the secretory stage of the endometrium in order to prepare the uterus for implantation and decreases the maternal immune response to allow for the body’s acceptance of pregnancy.[5,14] Moreover, this hormone thickens cervical mucus so it is impenetrable to sperm, inhibits lactation during pregnancy such that its fall after delivery triggers milk production, and decreases the contractility of the uterine smooth muscle. Overall, it is evident that a wide variety of hormonal and chemical changes occur in the female body as a result of menopause.

IMPLICATIONS OF OXIDATIVE STRESS IN MENOPAUSE

Oxidative stress plays an integral part of the aging process and results from the overproduction of free radicals such as reactive oxygen species (ROS), which overwhelm the body’s antioxidant defense mechanisms. Normally, antioxidants neutralize ROS and thus help to prevent over exposure from oxidative stress.[15,16] However, as the body ages, antioxidant levels decline, leaving the human body susceptible to a variety of age-related pathologies, such as non-alcoholic liver cirrhosis and atherosclerotic heart disease.[17,18] This decline combined with a gradual loss of estrogen in the female reproductive system is highly associated with the various sequelae of menopause such as heart disease, vasomotor disturbances, and osteoporosis.[18,19] The marked reduction in estrogen has been shown to increase levels of oxidative stress in the body, depending on the concentration and chemical structure of this hormone. Specifically, at high concentrations, estrogen tends to have a beneficial antioxidant effect by inhibiting the 8-hydroxylation of guanine DNA bases. However, at low concentrations, this hormone has pro-oxidant like effects, especially when its chemical structure contains a catechol. These effects include breaks in genetic material, formation of DNA adducts, and oxidation of bases.[20] Additionally, serum concentrations of inflammatory cytokines and pro-oxidant biomarkers such as glutathione, 4-hydroxynenal, and malonaldehyde were found to be higher in postmenopausal women than in premenopausal women.[21] The elevation of cytokines and pro-oxidant makers suggests that there is a high degree of oxidative stress in the postmenopausal state.[21,22]

Cardiovascular effects of menopause

Estrogen has been shown to play a physiologic role in the cardiovascular system by protecting against heart disease. This is facilitated via its atheroprotective effect on plaque stabilization and collateral vessel formation.[23,24] This hormone also has favorable effects on insulin, glucose, and lipoprotein levels in the serum.[24] However, because the antioxidant effect of estrogen is lost once women reach menopause, the incidence of atherosclerosis increases.[17] This is due to a variety of factors, one of which is a higher level of oxidized LDL in the blood.[21,24] Also, there is an overexpression of the angiotensin receptor, AT-I, in menopausal women, which contributes to the endothelial dysfunction and increased vasoconstriction seen in atherosclerosis.[25] Additionally, studies have shown that postmenopausal women have low levels (<1 μM) of nitric oxide, a natural vasodilator in the body. Such low levels have been shown to play a role in cardiovascular disease by allowing for more smooth muscle proliferation, inflammation, and atherogenic effects on the vasculature.[26,27] The higher levels of nitric oxide normally seen in premenopausal women provide cardioprotective effects and inhibit the propagation of smooth muscle typically seen in heart disease.[27] Furthermore, the marked reduction of estrogen during menopause increases free fatty acid levels. This makes postmenopausal women more susceptible to the metabolic syndrome and insulin resistance, both of which are implicated as risk factors for cardiovascular disease.[28] Thus, it is evident that the effects of declining estrogen and other substances during menopause can predispose women to cardiovascular disease.

Vasomotor disturbances

Oxidative stress is also involved in the pathogenesis of menopausal symptoms, such as vasomotor disturbances. These disturbances include hot flashes or night sweats. Hot flashes are defined as a sudden feeling of warmth usually over the face, neck, and chest. During a hot flash, the metabolic rate temporary increases, which often results in sweating, panic, and irritability.[29,30] Throughout menopause, there are repeated episodes of such vasomotor disturbances, which results in a prolonged increase of the metabolic rate. This increase has been show to contribute to the formation of oxidative stress by placing a hindrance on antioxidants and their function in neutralizing ROS.[29]

Osteoporosis

Osteoporosis is defined as a reduction in bone mineral density, which occurs when there is an imbalance between the creation of new bone and removal of old bone. A decline in estrogen has been shown to play a major role in this decreased bone mass during the onset of menopause, especially because it has a variety of protective effects on bone marrow and bone cells.[31,32] This can be seen via estrogen’s significant impact on bone-resorbing osteoclasts, which are cells involved in the breakdown of organic bone and removal of mineralized matrix. In particular, this hormone allows for increased bone formation by reducing the production and function of these osteoclasts as well as increasing osteoclast apoptosis. This effect on the osteoclastic cells of the bone is facilitated via estrogen’s inhibition of two signaling molecules, RANKL and CSF-1, which are involved in osteoclast differentiation and survival.[31,32,33,34] However, due to the estrogen deficiency during menopause, this beneficial effect on the bone is lost.

As stated earlier, the menopause induced hormonal deficit has been linked to an increase in inflammatory cytokines within the serum such as tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, and IL-12. These cytokines stimulate osteoclast and osteoblast formation, leading to increased bone turnover and eventually, bone loss.[22] Specifically, TNF-α, produced from macrophages and granulocytes, negatively impacts the bone by contributing to increased osteoclast formation. This occurs via direct stimulation of pro-osteoclastogenic activity of stromal cells.[22] Additionally, the high levels of FSH during menopause stimulate osteoclast differentiation and TNF-α production, both of which play an important role in osteoporotic bone loss.[35] Overall, it is evident from the role of pro-inflammatory cytokines and estrogen in bone remodeling that oxidative stress is a major contributor to bone density loss in osteoporosis.

Effects of oxidative stress on menopause

In healthy, premenopausal women there is usually an appropriate balance between free radical species and antioxidant mechanisms. As such, the level of oxidative stress in these women is not sufficient enough to affect the ovaries until the onset of menopause. In the aforementioned paragraphs, it has been stated that menopause creates a pro-oxidant state in the body due to the decline of the natural antioxidant, estrogen.[9,15] Consequently, the question often arises if oxidative stress can lead to menopause. The majority of studies have shown that oxidative stress alone in premenopausal women cannot induce menopause, but rather can lead to a variety of pathologies. Specifically, studies have reported that oxygen radicals have an important physiologic role within the ovary. However, the continuous synthesis of these harmful agents over time may lead to an increased cumulative risk of ovarian pathology. This includes premature ovarian failure, which is suggested to be exacerbated under conditions of reduced antioxidant status such as infection and autoimmune disease.[36]

TREATMENT OPTIONS FOR MENOPAUSE

Menopausal hormone therapy

MHT has been extensively researched as a potential treatment for the debilitating symptoms and sequelae of menopause. The aim of hormonal therapy is to enhance antioxidant defense mechanisms and decrease levels of oxidative stress in postmenopausal women.[37] A variety of researchers have found an association between MHT and its beneficial effect on oxidative stress. As such, most studies favor its administration to menopausal women. However, due to the fact estrogen has antioxidant and pro-oxidant characteristics, as well as a multitude of adverse side effects, some studies have not approved its use for the treatment of menopausal symptoms. A few studies even suggest that MHT has no significant effects on oxidative stress levels.[38,39]

Hormonal therapy has been shown to improve a variety of menopause-induced pathologies in the body, such as atherosclerotic heart disease. Specifically, the estrogen-progestin pill has been shown to reduce the risk of cardiovascular disease by opposing atherosclerosis. This is carried out via estrogen’s downregulation of inflammatory markers such as chemokines and cell adhesion molecules.[24] Furthermore, it has been shown to potentially stabilize atherosclerotic plaques by reducing the expression of matrix metalloproteinases and the production of plasminogen activator inhibitor-1.[40] MHT also aids the cardiovascular system by downregulating both angiotensin receptor gene expression and smooth muscle proliferation. The former effect helps to lower blood pressure, while the latter aids in the prevention of atherogenesis. Additionally, the high concentrations of estrogen in MHT promote the dilation of vessels through the production of prostacyclin, inhibition of endothelin synthesis, and blockage of calcium channels.[40,41]

In addition to its advantageous effect on the cardiovascular system, hormonal therapy has been shown to have a similar effect on vasoactive biomarkers. For example, a study conducted on healthy postmenopausal women demonstrated that MHT given for 1 year significantly reduced levels of catecholamines, mean blood pressure, and LDL cholesterol while increasing levels of nitrite and nitrate. This suggests that MHT has a cardiovascular benefit in those who are menopausal.[38] Interestingly, it also showed that the amount of oxidative stress in the body was not greatly altered by 12 months of MHT usage. This was measured via the oxidative stress biomarker 8-epi PGF, which did not significantly differ from its baseline value.[38] Other studies discussing the effect of hormonal therapy on oxidative stress showed decreases in serum lipid peroxides and upregulation of overall antioxidant status. Overall, it is clear that a definitive relationship exists between MHT and oxidative stress levels; however, the nature of this relationship cannot be confirmed.[42,43]

There are a considerable number of risks and side effects associated with MHT. These include increased risk of a pulmonary venous embolism, stroke, and cardiovascular events as well as a high incidence of estrogen-dependent breast, ovarian, and endometrial cancers.[39] It has been suggested that there is a certain window during the postmenopausal period in which MHT is most beneficial. Outside this time frame, estrogen intake can have detrimental effects on the body. The timing of MHT is crucial because the longer menopause continues, the greater the estrogen deficiency, which leads to a decreased activity of estrogen receptors. This reduced receptor activity, in turn, leads to severe endothelial dysfunction and eventually decreased vascular responsiveness as well as decreased effectiveness of MHT.[44]

Overall, current research indicates that postmenopausal women should use the lowest possible dose of MHT due to the aforementioned side effects.[45] However, long-term use of MHT may prevent cardiovascular disease if started in women at the onset of menopause. As such, the benefits of this pharmacotherapy seem to outweigh the risks for women under 60-year-old.[46]

Selective estrogen receptor modulators

SERMs are a class of compounds that act on the estrogen receptor, exhibiting agonistic actions of estrogen in some tissues and antagonistic actions in others. Two examples of SERMs are raloxifene and tamoxifen.[47] The former drug has antagonistic action in the uterus and breast, but agonistic action on the bone. Thus, the main use of raloxifene is to prevent and treat osteoporosis. Tamoxifen, however, acts as an agonist of estrogen receptors in the uterus but has antagonistic effects on the breast. Thus, its main use is to treat breast cancer. Similar to estrogen, raloxifene acts as an antioxidant due to the phenolic rings comprising its chemical structure.[47,48] Specifically, raloxifene’s mechanism of action aims at decreasing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, an enzyme that produces free radical species. This is facilitated via the downregulation of rac1 protein, which is required for NAPH oxidase activation.[49]

Additional beneficial effects of this SERM includes an increase in superoxide dismutase levels, a free radical scavenger, an increase in nitric oxide release, and a compound that suppresses smooth muscle proliferation and atherogenesis. Furthermore, raloxifene improves the lipid profile by preventing macrophage lipid oxidation and it also decreases levels of pro-oxidant biomarkers with the blood, such as malonaldehyde.[49,50] Additionally, raloxifene may play a protective role in the cardiovascular system by improving endothelial function and decreasing blood pressure levels as demonstrated in a study conducted on hypertensive rats.[50] Overall, by targeting the estrogen-mediated pathways, harmful results of oxidative stress can be prevented in postmenopausal women.

Exercise

Exercise has been shown to modulate levels of oxidative stress within the body through a variety of mechanisms. Studies have reported transient increases in ROS concentrations following acute aerobic and anaerobic exercise. However, this increased oxidative stress may serve as a necessary signal for upregulation of antioxidant defense mechanisms and eventual reduction of free radical species.[50,51] Specifically, exercise training has been associated with reduced basal oxidant production and free radical leak during oxidative phosphorylation, both of which contribute to the high oxidative stress levels seen during menopause.[51] Moreover, physical activity has been shown to alleviate menopausal symptoms and sequelae, such as sweating, anxiety, depression, hot flashes, osteoporosis, and cardiovascular disease.[52,53] In particular, one study reported that postmenopausal women had higher levels of oxidative stress associated with increased fat content than women who were premenopausal. Therefore, exercise in this population is helpful to reduce body fat, which is highly beneficial in augmenting the antioxidant capacity of the body.[54,55] Overall, exercise has been proven to be a valuable, cost-effective option in alleviating menopausal symptoms and improving the redox balance in healthy, postmenopausal women.[7]

DIETARY TREATMENT OF MENOPAUSE

Consumption of foods rich in antioxidants may be helpful in enhancing the beneficial effects of pharmacotherapy for postmenopausal patients.[56,57] Specifically, women who cannot tolerate the adverse side effects of MHT or are prone to develop estrogen-dependent breast cancer may find it advantageous to use dietary antioxidants to control the symptoms of menopause. Supplementation with antioxidants will not only improve the quality of life of menopausal women exposed to high amounts of oxidative stress, but also from other lifestyle-related factors such as smoking, stress, excessive alcohol consumption, and unhealthy eating habits.[57] The following antioxidants were found to be beneficial to women in the perimenopausal and postmenopausal phases: Vitamin C, Vitamin E, phytoestrogens, melatonin, Acanthopanax senticosus, klamin, Curcuma longa, grape polyphenols, and lycopene. Only the most relevant antioxidants will be discussed.

Vitamin C and E

Two dietary vitamins, vitamin C (ascorbic acid) and E (α-tocopherol), can be used to thwart the onset of various disorders associated with an age-related decrease in estrogen. Rich in their antioxidant capacity, these vitamins scavenge free radicals and neutralize oxidative stress.[58] One study assessing the effect of these vitamins on postmenopausal women found higher levels of the oxidative stress marker, malonaldehyde, and lower levels of the antioxidant enzymes, catalase and superoxide dismutase, in those who did not incorporate vitamin C and E in their diet.[59] These vitamins were not only helpful in achieving a favorable redox balance in the body, but they also are associated with a reduced risk of cardiovascular disease. This is mediated via their inhibition of cholesterol synthesis and LDL-cholesterol oxidation.[58,60]

In regards to the symptoms of menopause, both vitamins have been shown to reduce the intensity and number of hot flashes via promotion of adrenal function. This allows for increased hormonal production, specifically estrogen, allowing for a greater antioxidant defense system in postmenopausal women. When considering vitamin C alone, its intake has been associated with a protective effect on bone. This can be seen through its suppressive action on osteoblast and osteoclast activity, which thereby prevents accelerated bone turnover and eventual bone loss.[61,62]

However, at high doses, vitamin C and E have deleterious effects on the body. Specifically, large quantities of vitamin C (>2,000 mg/day) have been suggested to cause diarrhea, abdominal cramps, bloating, nausea, vomiting, and kidney stones.[61] While high doses of vitamin E (>1,000 mg/day) may increase the risk of bleeding by having an anticoagulant-like effect on the body and may also increase the risk of birth defects. Thus, when using vitamin C and E to quell the adverse effects of menopause, it is important that appropriate dosages be used.[56]

CONCLUSION

Within the female reproductive system, menopause is a key physiological phenomenon associated with eventual cessation of ovarian function and thus, the menstrual cycle. During this time period, estrogen becomes deficient, which is an established antioxidant in the body. This leads to oxidative stress in various tissues due to the release of ROS, leading to the development of a variety of symptoms and pathologies that characterize menopause. Specifically, oxidative stress has been linked to an increased risk of osteoporosis and cardiovascular disease and a greater frequency of vasomotor symptoms. Therefore, a multitude of therapies have been employed to target this estrogen deficit and unfavorable redox balance, the most promising of which are MHT therapy and SERMs. However, for those who cannot tolerate the adverse side effects of these pharmacological therapies, exercise and antioxidant supplementation can also be used to quell the symptoms of menopause. However, further investigation needs to be done regarding the efficacy and safety of these various treatments when used in clinical practice. Overall, because a wide variety of treatment options are now available to prevent and reverse the negative effects of oxidative stress associated with reproductive aging, the specific treatment selected should be chosen based on the history and clinical presentation of the patient.

TAKE HOME MESSAGE

Though the levels of oxidative stress rise inevitably in menopause due to declining levels of estrogen, this article has put forth methods that women can use to curb the deleterious sequelae effects of this condition.

Footnotes

Source of Support: Support is from the Center for Reproductive Medicine, Glickman Urological and Kidney Institute, Cleveland Clinic

REFERENCES

  1. Mishra GD, Kuh D. Health symptoms during mid-life in relation to menopausal transition: British prospective cohort study. BMJ. 2011;344:e402. [PMC free article] [PubMed]
  2. te Velde ER, Scheffer GJ, Dorland M, Broekmans FJ, Fauser BC. Developmental and endocrine aspects of normal ovarian aging. Mol Cell Endocrinol. 1998;145:67–73. [PubMed]
  3. Li Q, Geng X, Zheng W, Tang J, Xu B, Shi Q. Current understanding of ovarian aging. Sci China Life Sci. 2012;55:659–69. [PubMed]
  4. Djahanbakhch O, Ezzati M, Zosmer A. Reproductive ageing in women. J Pathol. 2007;211:219–31.[PubMed]
  5. Fitzgerald C, Zimon AE, Jones EE. Aging and reproductive potential in women. Yale J Biol Med. 1988;71:367–81. [PMC free article] [PubMed]
  6. Hoffman B, Schorge J, Halvorson L, Bradshaw K, Cunningham F. 2nd ed. New York City: The McGraw Hill Companies; 2012. William’s Gynecology; pp. 1–1399.
  7. Gudmundsdottir SL, Flanders WD, Augestad LB. Physical activity and cardiovascular risk factors at menopause: The Nord-trøndelag health study. Climacteric. 2013 [PubMed]
  8. Welt CK, McNicholl DJ, Taylor AE, Hall JE. Female reproductive aging is marked by decreased secretion of dimeric inhibin. J Clin Endrocrinol Metab. 1999;84:105–11. [PubMed]
  9. Rannevik G, Jeppsson S, Johnell O, Bjerre B, Laurell-Borulf Y, Svanberg L. A longitudinal study of the perimenopausal transition: Altered profiles of steroid and pituitary hormones, SHBG, and bone mineral density. Maturitas. 1995;21:103–13. [PubMed]
  10. Velarde MC. Pleiotropic actions of estrogen: A mitochondrial matter. Physiol Genomics. 2013;45:106–9. [PMC free article] [PubMed]
  11. Merlotti D, Gennari L, Stolakis K, Nuti R. Aromatase activity and bone loss in men. J Osteoporos 2011. 2011 230671. [PMC free article] [PubMed]
  12. Sluijmer AV, Heineman MJ, Koudstaal J, Theunissen PH, de Jong FH, Evers JL. Relationship between ovarian production of estrone, estradiol, testosterone, and androstenedione and the ovarian degree of stromal hyperplasia in postmenopausal women. Menopause. 1998;5:207–10. [PubMed]
  13. Cooke PS, Naaz A. Role of estrogens in adipocyte development and function. Biol Med (Maywood) 2004;229:1127–35. [PubMed]
  14. Dodd JM, Crowther CA. The role of progesterone in the prevention of preterm birth. Int J Womens Health. 2009;1:73–84. [PMC free article] [PubMed]
  15. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The role of oxidative stress of female reproduction: A review. Reprod Biol Endrocrinol. 2012;10:1–32.
  16. Ruder EH, Hartman TJ, Bumberg J, Goldberg MB. Oxidative stress and antioxidants: Exposure and impact on female infertility. Hum Reprod Update. 2008;14:345–57. [PMC free article] [PubMed]
  17. Witteman JC, Grobbee DE, Kok FJ, Hofman A, Valkenburg HA. Increased risk of atherosclerosis in women after the menopause. BMJ. 1989;298:642–4. [PMC free article] [PubMed]
  18. Becker BN, Himmelfarb J, Henrich WL, Hakim RM. Reassessing the cardiac risk profile in chronic hemodialysis patients: A hypothesis on the role of oxidant stress and other non-traditional cardiac risk factors. J Am Soc Nephrol. 1997;8:475–86. [PubMed]
  19. Bittner V. Menopause, age, and cardiovascular risk: A complex relationship. J Am Coll Cardiol. 2009;54:2374–75. [PubMed]
  20. Wang Z, Chandrasena ER, Yuan Y, Peng KW, van Breemen RB, Thatcher GR, Bolton JL. Redox cycling of catechol estrogens generating apurinic/apyrimidinic sites and 8-oxo-deoxyguanosine via reactive oxygen species differentiates equine and human estrogens. Chem Res Toxicol. 2010;23:1365–73.[PMC free article] [PubMed]
  21. Signorelli SS, Neri S, Sciacchitano S, Pino LD, Costa MP, Marchese G, et al. Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas. 2006;53:77–82. [PubMed]
  22. McLean RR. Proinflammatory cytokines and osteoporosis. Curr Osteoporos Rep. 2009;7:134–9.[PubMed]
  23. McCrohon JA, Nakhla S, Jessup W, Stanley KK, Celermajer DS. Estrogen and progesterone reduce lipid accumulation in human monocyte-derived macrophages: A sex-specific effect. Circulation. 1999;100:2319–25. [PubMed]
  24. Tchernof A, Calles-Escandon J, Sites CK, Poehlman ET. Menopause, central body fatness, and insulin resistance: Effects of hormone-replacement therapy. Coron Artery Dis. 1998;9:503–11. [PubMed]
  25. Arnal JF, Scarabin PY, Tremollieres F, Laurell H, Gourdy P. Estrogens in vascular biology and disease: Where do we stand today? Curr Opin Lipidol. 2007;18:554–60. [PubMed]
  26. Cohen RA. The role of nitric oxide and other endothelium-derived vasoactive substances in vascular disease. Prog Cardiovasc Dis. 1995;38:105–28. [PubMed]
  27. Moncada S, Palmer RM, Higgs EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43:109–42. [PubMed]
  28. O’Sullivan AJ, Martin A, Brown MA. Efficient fat storage in premenopausal women and in early pregnancy: A role for estrogen. J Clin Endocrinol Metab. 2001;86:4951–6. [PubMed]
  29. Kronenberg F. Hot flashes: Epidemiology and physiology. Ann N Y Acad Sci. 2006;592:52–86.[PubMed]
  30. Freedman RR. Biochemical, vascular, and metabolic mechanisms in menopausal hot flashes. Fertil Steril. 1998;70:332–7. [PubMed]
  31. Farr JN, Khosla S, Miyabara Y, Miller VM, Kearns AE. Effects of estrogen with micronized progesterone on cortical and trabecular bone mass and microstructure in recently postmenopausal women. J Clin Endocrinol Metab. 2013;98:E249–57. [PMC free article] [PubMed]
  32. Gallet M, Saïdi S, Haÿ E, Photsavang J, Marty C, Sailland J, et al. Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency. PLoS One. 2013;8:e54837.[PMC free article] [PubMed]
  33. Blair HC, Zaidi M. Osteoclastic differentiation and function regulated by old and new pathways. Rev Endocr Metab Disord. 2006;7:23–32. [PubMed]
  34. Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, et al. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood. 2005;106:852–9. [PubMed]
  35. Cervellati C, Bonaccorsi G, Cremonini E, Bergamini CM, Patella A, Castaldini C, et al. Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women. Clin Chem Lab Med. 2012;51:333–8. [PubMed]
  36. Behrman HR, Kodaman PH, Preston SL, Gao S. Oxidative stress and the ovary. J Soc Gynecol Investig. 2001;8(1 Suppl Proceedings):S40–2. [PubMed]
  37. Mueck AO, Seeger H. Estrogens acting as cardiovascular agents: Direct vascular actions. Curr Med Chem Cardiovasc Hemtaol Agents. 2004;2:35–42. [PubMed]
  38. Bednarek-Tupikowska G, Tworowska U, Jedrychowska I, Radomska B, Tupikowski K, Bidzinska-Speichert B, et al. Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme system in postmenopausal women. Clin Endocrinol (Oxf) 2006;64:463–8. [PubMed]
  39. Clarkson TB, Meléndez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: Its origin, current status, and future. Menopause. 2013;3:342–53. [PubMed]
  40. Gyglewski RJ. Prostacyclin and nitric oxide. Acta Haemtatol Pol. 1994;25(2 Suppl 2):75–81.[PubMed]
  41. Maffei S, Mercuri A, Prontera C, Zucchelli GC, Vassalle C. Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy. Climacteric. 2006;9:452–8. [PubMed]
  42. Bednarek-Tupikowska G, Tupikowski K, Bidzinska B, Bohdanowicz-Pawalak A, Antonowicz-Juchniewica J, Kosowska B, et al. Serum lipid peroxides and total antioxidant status in postmenopausal women on hormone replacement therapy. Gynecol Endrocrinol. 2004;19:57–63. [PubMed]
  43. Jacobsen AF, Sandset PM. Venous thromboembolism associated with pregnancy and hormonal therapy. Best Pract Res Clin Haematol. 2012;25:319–32. [PubMed]
  44. MacLennan AH, MacLennan A, Wenzel S, Chambers HM, Eckert K. Continuous low-dose oestrogen and progestogen hormone replacement therapy: A randomised trial. Med J Aust. 1993;159:102–6.[PubMed]
  45. Rozenberg S, Vandromme J, Antoine C. Postmenopausal hormone therapy: Risks and benefits. Nat Rev Endocrinol. 2013;9:216–27. [PubMed]
  46. Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stress: A 30 year history. Dyn Med. 2009;8:1. [PMC free article] [PubMed]
  47. Dutertre M, Smith CL. Molecular mechanisms of selective estrogen receptor modulator (SERM) action. J Pharmacol Exp Ther. 2001;295:431–7. [PubMed]
  48. Jordan CV. Antiestrogenic action of raloxifene and tamoxifene: Today and tomorrow. J Natl Cancer Inst. 1998;90:967–71. [PubMed]
  49. Wassmann S, Laufs U, Stamenkovic D, Linz W, Stash JP, Ahlbory K, et al. Raloxifene improves endothelial dysfunction in hypertension by reduced oxidative stress and enhanced nitric oxide production. Circulation. 2002;105:2083–91. [PubMed]
  50. Wassmann S, Wassmann K, Nickenig G. Modulation of oxidant and antioxidant enzyme expression function in vascular cells. Hypertension. 2004;44:381–6. [PubMed]
  51. Leeuwenburgh C, Heinecke JW. Oxidative stress and antioxidants in exercise. Curr Med Chem. 2001;8:829–38. [PubMed]
  52. Villaverde GC, Torres LG, Ábalos GM, Argente del Castillo MJ, Guisado IM, Guisado BR, et al. Influence of exercise on mood in postmenopausal women. J Clin Nurs. 2012;21:923–8. [PubMed]
  53. Davis SR, Castelo-Branco C, Chedraui P, Lumsden MA, Nappi RE, Shah D, et al. Understanding weight gain at menopause. Climacteric. 2012;15:419–29. [PubMed]
  54. Attipoe S, Park JY, Fenty N, Phares D, Brown M. Oxidative stress levels are reduced in postmenopausal women with exercise training regardless of hormone replacement therapy status. J Women Aging. 2008;54:11–9. [PubMed]
  55. Bloomer RJ. Effective exercise on oxidative stress biomarkers. Adv Clin Chem. 2008;46:1–50.[PubMed]
  56. Kushi LH, Folsom AR, Prinease RJ, Mink PJ, Wu Y, Bostick RM. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996;334:1156–62.[PubMed]
  57. Miguel J, Ramirez-Bosca A, Ramirez-Bosca JV, Alperi JD. Menopause: A review on the role of oxygen stress and favorable effects of dietary antioxidants. Arch Gerontol Geriatr. 2006;42:289–306.[PubMed]
  58. Cook NR, Albert CM, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: Results from the women’s antioxidant cardiovascular study. Arch Intern Med. 2007;167:1610–8.[PMC free article] [PubMed]
  59. Mlakar SJ, Osredkar J, Prezelj J, Marc J. Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women: A genetic association analysis. Menopause. 2012;19:368–76. [PubMed]
  60. Abdollahzad H, Eghtesadi S, Nourmohammadi I, Khadem-Ansari M, Nejad-Gashti H, Esmaillzadeh A. Effect of vitamin C supplementation on oxidative stress and lipid profiles in hemodialysis patients. Int J Vitam Nutr Res. 2009;79:281–7. [PubMed]
  61. McSorely PT, Young IS, Bell PM, Fee JP, McCance DR. Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women. Climacteric. 2003;6:238–47. [PubMed]
  62. Morton DJ, Barrett-Connor EL, Schneider DL. Vitamin C supplement use and bone mineral density in postmenopausal women. J Bone Miner Res. 2001;16:135–40. [PubMed]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952404/