BHRT Abstracts and Reviews

May 8, 2021

What is BHRT @ MedStudio?

An individualized approach to hormone replacement therapy, using bioidentical hormone replacement therapy (BHRT), pinpoints a person’s exact hormone levels, and what hormones are needed to rebalance their hormone deficiency.

The difference between synthetic and biologically identical hormones is in the chemical structure and functionality. Biologically identical hormones have the same chemical structure as the hormones created naturally in the human body.

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Read the abstracts and reviews about  bioidentical hormone replacement therapy  (BHRT) or search the database below to find more articles.

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A PMID is the unique identifier number used in PubMed for each article. The PMID is assigned to each article record when it enters the PubMed system. An "in press" publication will not have one unless it is issued as an electronic pre-publication. The PMID# is always found at the end of a PubMed citation. PMIDs do not change over time or during processing and are never reused. To search in PubMed by PMID, enter the ID with or without the search field tag [pmid]. You can search for several PMIDs by entering each number in the search box separated by a space (e.g., 17170002 16381840); PubMed will or the PMIDs together. To search in combination with other terms, you must enter the search field tag, e.g., lipman[au] 16381840[pmid].

Search the PubMed Central database here

Postgrad Med. 2009 Jan;121(1):73-85.

The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Holtorf K. Holtorf Medical Group, Inc., Torrance, CA 90505. BACKGROUND: The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective. OBJECTIVE: This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease. METHODS: Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected. RESULTS: Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone. CONCLUSION: Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly. PMID: 19179815  

Curr Cardiol Rev. 2008 Nov;4(4):309-22.

Experimental benefits of sex hormones on vascular function and the outcome of hormone therapy in cardiovascular disease. Ross RL, Serock MR, Khalil RA. Division of Vascular Surgery, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts 02115. Abstract: Cardiovascular disease (CVD) is more common in men and postmenopausal women than premenopausal women, suggesting vascular benefits of female sex hormones. Experimental data have shown beneficial vascular effects of estrogen including stimulation of endothelium-dependent nitric oxide, prostacyclin and hyperpolarizing factor-mediated vascular relaxation. However, the experimental evidence did not translate into vascular benefits of hormone replacement therapy (HRT) in postmenopausal women, and HERS, HERS-II and WHI clinical trials demonstrated adverse cardiovascular events with HRT. The lack of vascular benefits of HRT could be related to the hormone used, the vascular estrogen receptor (ER), and the subject’s age and preexisting cardiovascular condition. Natural and phytoestrogens in small doses may be more beneficial than synthetic estrogen. Specific estrogen receptor modulators (SERMs) could maximize the vascular benefits, with little side effects on breast cancer. Transdermal estrogens avoid the first-pass liver metabolism associated with the oral route. Postmenopausal decrease and genetic polymorphism in vascular ER and post-receptor signaling mechanisms could also modify the effects of HRT. Variants of cytosolic/nuclear ER mediate transcriptional genomic effects that stimulate endothelial cell growth, but inhibit vascular smooth muscle (VSM) proliferation. Also, plasma membrane ERs trigger not only non-genomic stimulation of endothelium-dependent vascular relaxation, but also inhibition of [Ca(2+)]i, protein kinase C and Rho kinase-dependent VSM contraction. HRT could also be more effective in the perimenopausal period than in older postmenopausal women, and may prevent the development, while worsening preexisting CVD. Lastly, progesterone may modify the vascular effects of estrogen, and modulators of estrogen/testosterone ratio could provide alternative HRT combinations. Thus, the type, dose, route of administration and the timing/duration of HRT should be customized depending on the subject’s age and preexisting cardiovascular condition, and thereby make it possible to translate the beneficial vascular effects of sex hormones to the outcome of HRT in postmenopausal CVD. PMID: 20066139    

Maturitas. 2008 May 20;60(1):10-8. Epub 2008 Apr 14.

Metabolic syndrome after menopause and the role of hormones.

Lobo RA. Dept of Obstetrics & Gynecology, Columbia University College of Physicians & Surgeons, New York, NY 10032.

OBJECTIVES: The purpose of this review is to focus on the importance of metabolic syndrome (MBS) and its increased prevalence in postmenopausal (PM) women. Also the role of hormonal therapy in PM women with MBS will be discussed. METHODS: Review of the relevant literature and results from recent clinical trials. RESULTS: MBS may occur in 40% of PM women and is largely determined by overweight status and obesity. Weight gain, particularly an increase in central fat mass increases in PM women, beginning a few years prior to menopause. Hormonal Therapy (HT) in normal PM women, generally decreases abdominal fat, but the effect of transdermal estrogen is preferable to oral therapy in this regard. In women with MBS, oral therapy was found to increase leptin and the leptin/adiponectin ratio, while transdermal therapy showed no changes. HT has been found to improve insulin resistance in PM women, although the data are mixed. In women with MBS, oral therapy was found to worsen parameters of insulin resistance, while transdermal therapy had minimal effects overall. Women with MBS have elevations in several inflammation and coagulation factors. Both oral and transdermal HT reduce inflammation markers except for levels of CRP and MMP-9, which increase with oral therapy, but are unaffected by the transdermal route. Oral estrogen has a small pro-coagulant effect, not observed with transdermal therapy, in both normal PM women and those with MBS. The beneficial effects of HT on lipids occur in PM women with and without MBS, although the changes in the latter are minimal. Blood pressure was not affected by HT in women with MBS. CONCLUSIONS: Weight gain and obesity largely drives the increased prevalence of MBS in PM women. Use of HT is beneficial overall for reducing many of the parameters of MBS. Our own data would suggest that in MBS, transdermal therapy may be preferable to oral therapy, at least in standard doses. PMID: 18407440  

Clin Interv Aging. 2008;3(1):51-4.

Transdermal hormone therapy and bone health.

Shulman LP. Division of Reproductive Genetics, Department of Obstetrics and Gynecology, Feinberg School of Medicine of Northwestern University, Chicago, Illinois.

Abstract: The clinical aftermath of the reporting of the initial findings of the Women’s Health Initiative (WHI) in 2002 was a profound reduction in the use of hormone therapies by menopausal women. This reduction led to a well documented increase in vasomotor symptoms and vaginal atrophy among those women who discontinued their hormone regimens. However, another adverse impact among these women, as well as many other menopausal women, is the well recognized increased likelihood of osteoporosis resulting from the decline in circulating estradiol levels associated with natural and surgical menopause. Although the use ofnon-hormonal drugs such as bisphosphonates has been shown to reduce the risk of fracture in women with osteoporosis, bisphosphonates have not been shown to reduce the risk of fracture in non- osteoporotic women. Indeed, only oral estrogen (as demonstrated in the WHI studies) has been shown to reduce the risk of fracture in osteoporotic and non-osteoporotic women. As non-oral hormone therapies have been shown to be as effective in treating vasomotor symptoms and vulvovaginal atrophy and to have a different (and perhaps more beneficial) physiological effect than oral regimens, it behooves us to assess the impact of non-oral hormone regimens on bone mineral density and fracture risk. Although there are no clinical trials that primarily assess the impact of non-oral regimens on fracture risk in menopausal women, numerous studies are consistent in demonstrating the positive impact of non-oral regimens in maintaining and increasing bone mineral density among users, even for those women using estrogen doses that are considered to be “too low” to have a beneficial impact on other menopausal symptoms. PMID: 18488878  

Climacteric. 2006 Apr;9(2):108-18.

The long-term impact of 2-3 years of hormone replacement therapy on cardiovascular mortality and atherosclerosis in healthy women.

Alexandersen P, Tankó LB, Bagger YZ, Qin G, Christiansen C. Center for Clinical and Basic Research, Ballerup, Denmark.

OBJECTIVE: The effect of hormone replacement therapy (HRT) on cardiovascular risk is intensely debated. The aim of this study was to investigate the long-term effects of HRT given for a few years on all-cause and cardiovascular mortality and the severity of atherosclerosis. METHODS: This analysis was based on a cohort of 1,458 postmenopausal women (55.8 +/- 6.1 years old) who previously participated in a number of randomized, placebo-controlled, clinical trials assessing the efficacy of 2-3 years of therapy with various estrogen plus progestin combinations for preventing bone loss. Women were followed on average for 9.8 years and came for a follow-up visit. Outcome variables were all-cause and cardiovascular mortality and the severity of atherosclerosis, as estimated by semi-quantitative scoring of vascular calcification in the lumbar aorta on lateral radiographs. RESULTS: A total of 174 women died during the observation period. All-cause mortality was decreased by 30% in the HRT+ group compared with the HRT- group (hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.50-0.97) after adjusting for age, body mass index and smoking. Under the same conditions, similar results characterized mortality from cardiovascular disease (n = 61 deaths; 35.1% of all deaths) and coronary heart disease (n = 39 deaths; 22.4% of all deaths), which were decreased by 46% (HR 0.54, 95% CI 0.29-0.98, p = 0.045) and 53% (HR 0.47, 95% CI 0.21-1.03, p = 0.062), respectively. Furthermore, the mean severity score of aortic calcification at follow-up was significantly lower in hormone-treated compared to non-treated women (p < 0.0001). CONCLUSION: Women who receive 2-3 years of HRT after menopause do not have increased all-cause mortality, and results of the present study suggest relative cardiovascular benefits compared to those who had not used hormones. PMID: 16698657  

Altern Med Rev. 2006 Sep;11(3):208-23.

A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Moskowitz D. Moskowitz, Deborah. Wellness Designed, LLC. Abstract: Numerous forms of estrogens and progestins are utilized for the treatment of menopausal complaints and associated conditions that occur temporally. Although known to be different with respect to molecular structure, receptor affinity, metabolism, and other physiological traits, most have been treated as if they were clinically identical. The majority of these hormone preparations, commonly referred to as hormone replacement therapy (HRT), should perhaps be more aptly referred to as hormone substitution therapy, as most of the therapies utilized do not exactly match those produced in the body. Research indicates these synthetic hormones vary clinically in safety and efficacy. As such, women and their physicians have, in increasing numbers, been opting for the use of bioidentical hormones; i.e., those that match the structure and function of hormones produced in the body. With greater utilization and research surrounding bioidentical hormones, the differences can now begin to be fully assessed and appreciated. This article reviews the disparities between synthetic and bioidentical estrogens and progestins/progesterone with respect to safety and efficacy; special attention is devoted to clinical outcomes in the breast, endometrium, bone, cardiovascular system, and brain. The studies reviewed suggest bioidentical progesterone does not have a negative effect on blood lipids or vasculature as do many synthetic progestins, and may carry less risk with respect to breast cancer incidence. Studies of both bioidentical estrogens and progesterone suggest a reduced risk of blood clots compared to non-bioidentical preparations. Bioidentical hormone preparations have demonstrated effectiveness in addressing menopausal symptoms. The author advocates for continued research on bioidentical hormones and concludes there is currently sufficient evidence to support their preferred use over that of their synthetic cousins. PMID: 17217322  

Int J Fertil Womens Med. 2004 Nov-Dec;49(6):252-67.

A clinician’s review of the WHI-related literature.

Speroff L. Department of Obstetrics and Gynecology, Oregon Health Sciences University Portland, Oregon 97239. Abstract: When the monitoring board of the Women’s Health Initiative (WHI) canceled the estrogen-progestin arm of the study in July 2002, the effect was immediate and dramatic, as several million postmenopausal women with the full agreement of their physicians ceased taking combined hormone therapy. Soon thereafter the manufacturers of conjugated equine estrogens felt compelled to publicize a drastic restriction of the indications for their product. Little notice, except in the medical literature, was given to the continuation of the other treatment arms of the WHI, nor did the rather small (however significant) increases in risk of cardiovascular disease and breast cancer resulting from combined therapy receive widespread serious analysis. In this article, special attention is given to the population sampling involved in setting up the WHI, arm by arm, with full discussion of how these samplings compare with those in other studies--HERS, ERA, WEST, etc. All studies are scrutinized in terms of treatment regimens, follow-up, confounding factors, particularly statins and aspirin, and high drop-out rates in order to discover possible reasons for the results in the WHI for primary and secondary prevention of cardiovascular disease in the combined-therapy arm and slightly disappointing results for breast cancer. Each of the two main sections of the article, Cardiovascular Disease and Breast Cancer, concludes with a detailed summation of points derived from the often contrasting results of the various studies, which can be used in counseling patients. PMID: 15751264  

Climacteric. 2004 Dec;7(4):347-56.

Transdermal hormone therapy: gels and patches.

Samsioe G. Department of Obstetrics and Gynecology, Lund University Hospital, 221 85 Lund, Sweden.

Abstract: Hormone therapy (HT) in the climacteric has a number of beneficial effects including mitigation of climacteric symptoms and prevention of osteoporosis. Administration of HT via the transdermal route avoids hepatic first-pass metabolism and therefore the high plasma levels of estrogen metabolites that are associated with oral administration. Patch formulations have traditionally been the most common form of transdermal HT. However, as patches may be associated with local skin reactions, gel formulations have been developed in an attempt to improve acceptability and compliance with transdermal HT. Patch and gel formulations are equally as effective in treating climacteric symptoms and improving bone mineral density, and the effects are comparable to those achieved by oral HT. PMID: 15799606  

Clin Pharmacokinet. 2002;41(9):661-80.

Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications.

Zhang H, Zhang J, Streisand JB. Cephalon, Inc., Salt Lake City, Utah 84116, USA

Abstract: Oral mucosal drug delivery is an alternative method of systemic drug delivery that offers several advantages over both injectable and enteral methods. Because the oral mucosa is highly vascularised, drugs that are absorbed through the oral mucosa directly enter the systemic circulation, bypassing the gastrointestinal tract and first-pass metabolism in the liver. For some drugs, this results in rapid onset of action via a more comfortable and convenient delivery route than the intravenous route. Not all drugs, however, can be administered through the oral mucosa because of the characteristics of the oral mucosa and the physicochemical properties of the drug. Several cardiovascular drugs administered transmucosally have been studied extensively. Nitroglycerin is one of the most common drugs delivered through the oral mucosa. Research on other cardiovascular drugs, such as captopril, verapamil and propafenone, has proven promising. Oral transmucosal delivery of analgesics has received considerable attention. Oral transmucosal fentanyl is designed to deliver rapid analgesia for breakthrough pain, providing patients with a noninvasive, easy to use and nonintimidating option. For analgesics that are used to treat mild to moderate pain, rapid onset has relatively little benefit and oral mucosal delivery is a poor option. Oral mucosal delivery of sedatives such as midazolam, triazolam and etomidate has shown favourable results with clinical advantages over other routes of administration. Oral mucosal delivery of the antinausea drugs scopolamine and prochlorperazine has received some attention, as has oral mucosal delivery of drugs for erectile dysfunction. Oral transmucosal formulations of testosterone and estrogen have been developed. In clinical studies, sublingual testosterone has been shown to result in increases in lean muscle mass and muscle strength, improvement in positive mood parameters, and increases in genital responsiveness in women. Short-term administration of estrogen to menopausal women with cardiovascular disease has been shown to produce coronary and peripheral vasodilation, reduction of vascular resistance and improvement in endothelial function. Studies of sublingual administration of estrogen are needed to clarify the most beneficial regimen. Although many drugs have been evaluated for oral transmucosal delivery, few are commercially available. The clinical need for oral transmucosal delivery of a drug must be high enough to offset the high costs associated with developing this type of product. Drugs considered for oral transmucosal delivery are limited to existing products, and until there is a change in the in the selection and development process for new drugs, candidates for oral transmucosal delivery will be limited. PMID: 12126458    

Maturitas. 2001 Dec 14;40(3):195-201.

Hormone replacement therapy: the benefits in tailoring the regimen and dose.

Gambacciani M, Genazzani AR. Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology Piero Fioretti, University of Pisa, Via Roma 67, 56100 Pisa, Italy.

Abstract: Despite the clear benefits of long-term hormone replacement therapy (HRT), the majority of patients tend to undergo short-term treatment. The cyclical bleedings induced by the sequential progestogen administration are often unacceptable namely in the elderly postmenopausal women. At the standard doses HRT preparations can also induce annoying hormone-related side effects, both in sequential and continuous combined regimens. Lower HRT schedules are reported to be highly effective in the relief of climacteric symptoms, inducing minimal endometrial stimulation with high rates of amenorrhea. Continuous administration of low doses of progestins is safe for endometrium protection and minimizes progestin-related side effects. Indeed, it has been demonstrated that low dose HRT can prevent the increase in bone turnover and the consequent bone loss in postmenopausal women. The choice of lower HRT dosages can also be useful for the number of potential disadvantages of standard HRT doses, mainly for long-term treatments. Low dose regimens should be considered as a starting dose to minimize the occurrence of side effects, improving compliance and, therefore, HRT effects on the prevention of long-term consequences of estrogen deprivation. PMID: 11731180  

Maturitas. 2001 Oct 31;40(1):75-83.

Effects of hormonal replacement therapy in postmenopausal hypertensive patients.

Affinito P, Palomba S, Bonifacio M, Fontana D, Izzo R, Trimarco B, Nappi C. Clinical Department of Gynecology, Obstetrics, and Human Reproduction, Facoltà di Medicina e Chirurgia, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy.

OBJECTIVE: To evaluate the effect of hormonal replacement therapy (HRT) on blood pressure (BP) in postmenopausal hypertensive women. METHODS: Sixty women affected by hypertension were enrolled and randomized in two groups of treatment: transdermal continuous HRT in a sequential regimen (group A) and placebo (group P). At baseline, after 3 and 6 months of treatment, the BP with standard sphygmomanometer and with 24-h ambulatory recording method was evaluated in two periods (from day 10 through day 16 of the cycle and from day 20 through day 27 of the cycle). At the same time, we also evaluated total cholesterol, LDL-c, HDL-c, triglycerides, and fibrinogen levels. RESULTS: After 3 and 6 months of treatment, no significant variations of systolic and diastolic BP measured with standard sphygmomanometer were detected in both groups. On the contrary, in group A in comparison with basal values and group P, and without difference between the two phases of treatment, the 24-h recording showed a significant (P<0.05) decrease in BP. No significant variations were detected in group P versus baseline. In particular, we observed in group A at 3 months of treatment a significant (P<0.05) decrease only in daytime BP in comparison with basal values and group P, without difference between the two phases of treatment. Indeed, the decrease in daytime BP was significant (P<0.05) for both systolic and diastolic BP. At 3 and 6 months a significant (P<0.05) decrease in total cholesterol, LDL-c and fibrinogen levels was detected in group A versus baseline and group P. HDL-c and triglyceride concentrations showed no significant variations. CONCLUSIONS: The transdermal HRT induces a significant reduction of BP values and a favorable metabolic action in postmenopausal hypertensive patients. PMID: 11684376  

Diabetes Care. 2001 Jul;24(7):1144-50.

Hormone replacement therapy is associated with better glycemic control in women with type 2 diabetes: The Northern California Kaiser Permanente Diabetes Registry.

Ferrara A, Karter AJ, Ackerson LM, Liu JY, Selby JV; Northern California Kaiser Permanente Diabetes Registry. Division of Research, Kaiser Permanente, Oakland, California 94611.

OBJECTIVE: In women with diabetes, the changes that accompany menopause may further diminish glycemic control. Little is known about how hormone replacement therapy (HRT) affects glucose metabolism in diabetes. The aim of this study was to examine whether HbA(1c) levels varied by current HRT among women with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort of 15,435 women with type 2 diabetes who were members of a health maintenance organization, HbA(1c) and HRT were assessed by reviewing records in the health plan’s computerized laboratory and pharmacy systems. Sociodemographic and clinical information were collected by survey. RESULTS: The mean age was 64.7 years (SD +/- 8.7). The study cohort comprised 55% non-Hispanic whites, 14% non-Hispanic blacks, 12% Hispanics, 11% Asians, 4% “other” ethnic groups, and 4% with missing ethnicity data. Current HRT was observed in 25% of women. HbA(1c) levels were significantly lower in women currently using HRT than in women not using HRT (age-adjusted mean +/- SE: 7.9 +/- 0.03 vs. 8.5 +/- 0.02, respectively, P = 0.0001). No differences in HbA(1c) level were observed between women using unopposed estrogens and women using opposed estrogens. In a Generalized Estimating Equation model, which took into account patient clustering within physician and adjusted for age, ethnicity, education, obesity, hypoglycemic therapy, diabetes duration, self-monitoring of blood glucose, and exercise, HRT remained significantly and independently associated with decreased HbA(1c) levels (P = 0.0001). CONCLUSIONS: HRT was independently associated with decreased HbA(1c) level. Clinical trials will be necessary to understand whether HRT may improve glycemic control in women with diabetes. PMID: 11423493