Compounded Bioidentical Hormone Therapy Research Articles

Fear, misinformation, and pharmaceutical messianism in the promotion of compounded bioidentical hormone therapy.

Compounded bioidentical hormone therapy (cBHT) for menopausal symptoms maintains popularity in western countries despite the availability of hormone products in different formulations and dosages produced by pharmaceutical companies with federal oversight. Akin to many populist therapeutic trends in the history of medicine, cBHT advocates tend to capitalize on consumer fears about existing FDA-approved hormone treatments. Unsubstantiated, exaggerated, or outright false claims are commonplace in promoting cBHT. Given these elements, the basic elements of pharmaceutical messianism continue to drive the cBHT movement.

Part I: Interactive case: Menopause

Part I: Interactive case: Menopause

Concerns About Compounded Bioidentical Menopausal Hormone Therapy.

Following the release of the Women's Health Initiative data, women began to use compounded bioidentical hormone therapy (cBHT) in the misguided belief of greater safety and efficacy than traditional hormone therapy. New guidelines recommend government-approved hormone therapy for symptomatic healthy menopausal women younger than 60 years or within 10 years of menopause at the time of initiation. For women requesting bioidentical hormones, those similar to the hormones present before menopause, there are many government-approved hormone therapies with extensive pharmacokinetic, safety, and efficacy data provided with package inserts delineating efficacy, safety, and potential risks. For women requesting non-Food and Drug Administration-approved (cBHT), these cBHTs lack data on pharmacokinetics, safety, and efficacy and are not provided a label detailing risk. Their use should be restricted to women with allergies or dosing or formulations not available in government-approved therapies. Pellet therapy providing women with supraphysiologic hormone dosing raises even more safety concerns.

Safety and efficacy of compounded bioidentical hormone therapy (cBHT) in perimenopausal and postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

More information is needed about the efficacy and safety of compounded bioidentical hormone therapy (cBHT) in the published literature. A thorough synthesis of existing data is not currently available. To provide a systematic review and meta-analysis of the existing evidence related to the safety and efficacy of commonly prescribed cBHT preparations in perimenopausal and postmenopausal women. PubMed, ClinicalTrials.gov, and The Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) comparing cBHT with a placebo or FDA-approved products in perimenopausal or postmenopausal women were eligible. The risk of bias was assessed by the Cochrane risk of bias tool. The primary safety outcome was changes in lipid profile and glucose metabolism, and the primary efficacy outcome was the change of vaginal atrophy symptoms. The secondary outcomes included the change of endometrial thickness, risk of adverse events, vasomotor symptoms, change of serum hormone levels, and change of bone mineral density. A total of 29 RCTs reported in 40 articles containing 1,808 perimenopausal and postmenopausal women were included. Two risk factors of cardiovascular disease, lipid profile, and glucose metabolism, were evaluated with cBHT. The results showed that compounded androgen was not associated with change of lipid profile or glucose metabolism. There was no change in endometrial thickness or serious adverse events. There were more androgenic side effects with compounded dehydroepiandrosterone compared with placebo as expected. Other safety measures including clinical cardiovascular events, endometrial biopsy, and risk of breast cancer were not studied. cBHT in the form of compounded vaginal androgen was found to significantly improve vaginal atrophy symptoms (SMD -0.66 [95% CI, -1.28 to -0.04]; I2 = 86.70%). This finding was supported by the association between compounded vaginal androgen and improved female sexual function scores. The changes of serum hormone levels were also evaluated. Despite the variations in absorption from different types of compounded hormones, routes, and strengths, the trends were consistent with published data from FDA-approved products. This review found that cBHT used in primarily short-term RCTs is not associated with adverse changes in lipid profile or glucose metabolism. cBHT in the form of vaginal androgens appears beneficial for vaginal atrophy symptoms. There are insufficient RCTs of cBHT to assess clinical risk of breast cancer, endometrial cancer, or cardiovascular disease. Long-term studies with clinical endpoints are needed.

Compounded Bioidentical Hormones: Myths and Realities.

The spectacular success of compounded bioidentical hormone therapy is a product of the unanticipated negative-to-neutral findings of the Women's Health Initiative hormone trial and the peculiarities of their regulatory status. By not having to provide scientific evidence of safety and efficacy, a requirement for all Food and Drug Administration (FDA)-approved hormone therapy products, the industry's relatively unfettered marketing now accounts for about one third of menopausal hormone therapy prescriptions. Clinicians are often caught in the middle between patient beliefs and a desire to practice evidence-based medicine. Strategies are needed to redirect patients towards truly safe and effective treatment for their menopausal symptoms.

Compounded bioidentical hormone therapy: new recommendations from the 2020 National Academies of Sciences, Engineering, and Medicine.

Bioidentical hormones have the exact same chemical and molecular structure as hormones that are produced in the human body. Bioidentical hormones are available as FDA-approved hormone formulations. Nonapproved custom-compounded preparations are marketed as bioidentical, but content is uncertain. The widespread use of compounded bioidentical hormone therapy despite the lack of evidence to support its safety and efficacy is concerning. This Practice Pearl highlights the 2020 recommendations from the National Academies of Sciences, Engineering, and Medicine regarding the use of compounded bioidentical hormones.

Postmenopausal Hormone Therapy-Local and Systemic: A Pharmacologic Perspective.

Every woman, if she lives long enough, will transition into menopause, and as the US population ages, women will be spending more time in a postmenopausal state than before. For postmenopausal women, the decision to initiate menopausal hormone therapy should be individualized. A thorough evaluation of the patient's cardiovascular, venous thromboembolic, cancer, and fracture risk should be considered along with the woman's quality of life. Hormone therapy exerts its therapeutic effects on vasomotor symptoms, the skeleton, and the genitourinary system independent of age since menopause and these benefits are lost once hormone therapy is stopped. Here we review the pharmacologic properties dose, formulation, mode of administration, timing of initiation, and duration of hormonal therapies in regard to optimizing benefit and minimizing risk to the patient. This discussion will focus on the effects of common hormonal therapies including estrogen (local and systemic), progesterone, estrogen receptor agonist/antagonist, and local dehydroepiandrosterone and include a brief review of compounded bioidentical hormone therapy.

Uterine bleeding rates with hormone therapies in menopausal women with vasomotor symptoms

Introduction: Bleeding and spotting are major reasons why women discontinue use of hormone therapy (HT) taken to treat menopausal vasomotor symptoms (VMS). The REPLENISH trial (NCT01942668) evaluated TX-001HR (TherapeuticsMD, Boca Raton, FL), a single oral capsule containing bioidentical 17β-estradiol (E2) and progesterone (P4), for treating moderate to severe menopausal VMS in women with a uterus; the 1 mg E2/100 mg P4 dose was recently approved as Bijuva™ by the US Food and Drug Administration (FDA; October 2018). This report compares the incidence of uterine bleeding with TX-001HR to other FDA-approved menopausal HT and unapproved compounded bioidentical HT (CHT).

Why women choose compounded bioidentical hormone therapy: lessons from a qualitative study of menopausal decision-making

BackgroundIn recent years, compounded bioidentical hormone therapy (CBHT) has emerged as a popular alternative to manufactured, FDA approved hormone therapy (HT)—despite concerns within the medical community and the availability of new FDA approved “bioidentical” products. This study aims to characterize the motivations for using CBHT in a U.S. sample of ordinary midlife women.MethodsWe analyze data collected from 21 current and former users of CBHT who participated in a larger qualitative study of menopausal decision-making among U.S. women. Interviews and focus groups were audio-recorded, transcribed verbatim, and analyzed thematically using an iterative inductive and deductive process.ResultsAlthough women’s individual motivations varied, two overarching themes emerged: “push motivations” that drove women away from conventional HT and from alternative therapies, and “pull motivations” that attracted women to CBHT. Push motivations focused on (1) fear and uncertainty about the safety of conventional HT, (2) an aversion to conjugated estrogens in particular, and (3) and overarching distrust of a medical system perceived as dismissive of their concerns and overly reliant on pharmaceuticals. Participants also voiced dissatisfaction with the effectiveness of herbal and soy supplements. Participants were attracted to CBHT because they perceive it to be (1) effective in managing menopausal symptoms, (2) safer than conventional HT, (3) tailored to their individual bodies and needs, and (4) accompanied by enhanced clinical care and attention.ConclusionsThis study finds that women draw upon a range of “push” and “pull” motivations in their decision to use CBHT. Importantly, we find that women are not only seeking alternatives to conventional pharmaceuticals, but alternatives to conventional care where their menopausal experience is solicited, their treatment goals are heard, and they are engaged as agents in managing their own menopause. The significance of this finding goes beyond understanding why women choose CBHT. Women making menopause treatment decisions of all kinds would benefit from greater shared decision-making in the clinical context in which they are explicitly invited to share their experiences, priorities, and preferences. This would also provide an opportunity for clinicians to discuss the pros and cons of conventional HT, CBHT, and other approaches to managing menopause.

REPLENISH trial: Endometrial protection with a 17β-estradiol and progesterone combination (TX-001HR) in postmenopausal women with vasomotor symptoms

Introduction: TX-001HR (TherapeuticsMD, Inc., Boca Raton, FL) is an investigational hormone therapy (HT) of combined naturally occurring 17β-estradiol and progesterone (which some call bio-identical) in a single, oral softgel capsule developed to treat menopause-related vasomotor symptoms (VMS). More than 3 M women are estimated to use unapproved compounded bio-identical HT (BHT) in the US, and it is also used outside of the US. Compounded BHT may be associated with endometrial cancer.

Use of Compounded Bioidentical Hormone Therapy in Menopausal Women: An Opinion Statement of the Women's Health Practice and Research Network of the American College of Clinical Pharmacy

Menopausal symptoms affect a significant portion of women. Traditional treatment with manufactured hormone therapy can alleviate these symptoms, but many women and their health care providers are concerned about the risks, such as venous thromboembolism and certain types of cancer, demonstrated with manufactured hormone therapy. Compounded bioidentical hormone therapy has been proposed and is often used as a solution for these concerns. Despite this use, no data are currently available to support the claims that compounded bioidentical hormone therapy is a safer or more efficacious option compared with manufactured hormone therapy. A common misperception is that all manufactured products consist of synthetic hormones and all compounded medications consist of natural hormones; however, in fact, significant overlap exists. Several key stakeholder organizations have issued statements expressing concern about the lack of evidence regarding the efficacy and safety of compounded bioidentical hormone therapy, in addition to concerns regarding prescribing patterns. The Women's Health Practice and Research Network of the American College of Clinical Pharmacy recommends against the consistent use of compounded bioidentical hormones as a safer option compared with manufactured therapy and supports the statements of other key organizations, acknowledging the need for more robust clinical studies to evaluate the potential advantages and disadvantages of compounded bioidentical products compared with manufactured products.

Beliefs about bioidentical hormone therapy: A cross-sectional survey of pharmacists

ObjectiveThe aim of this study was to assess pharmacists’ beliefs about bioidentical hormone therapy (BHT) and to identify factors influencing these beliefs. Study designThis was a cross-sectional survey of pharmacists. An email invitation to participate in the online survey was sent to a random sample of 2000 pharmacists in Alberta. The survey was accessible for a six-week period from May to July, 2011. A 54-item questionnaire was used to capture knowledge and beliefs about, and confidence in BHT. Summary statistics and multivariate regression were used for analyses. ResultsOverall, 401 pharmacists completed the survey (response rate 20%). Respondents were mainly female (64%), above 30 years of age (81%) and in practice for more than 10 years (63%). Only 35% of respondents correctly classified BHT as including both compounding and commercial products. In regards to beliefs, 68% of respondents agreed that BHT is as effective as non-bioidentical hormones for vasomotor symptoms, while 60% agreed BHT had equal risk. Beliefs on estriol, progesterone, and saliva testing however, were more diverse with many “do not know” responses (40%). In multivariate analysis, pharmacists who worked in pharmacies that compounded BHT were more likely to believe in BHT safety (p<0.001), and have greater confidence with BHT (p<0.001). ConclusionsResults from this survey indicated that pharmacists had varying beliefs on BHT. In addition, beliefs on the safety of BHT were associated with pharmacists’ practice, specifically working in a pharmacy that compounds BHT. This study helps identify areas for targeted education.

Bioidentical Hormone Therapy: A Review of the Evidence

Bioidentical hormone therapy (BHT) uses bioidentical hormones (BHs), derivatives of plant extracts chemically modified to be structurally indistinguishable from human endogenous hormones. BHTs are available commercially or can be compounded into different dosages and for different routes of administration. Typically, compounded preparations of BHs may include estriol, estrone, estradiol, testosterone, micronized progesterone, and occasionally dehydroepiandrosterone (DHEA). It is generally accepted that estrogen-based hormone therapies share similar efficacies as well as risks. Many FDA-approved and regulated pharmaceutically manufactured and branded conventional hormone therapies (CHTs) employ BHs. Since the publication of the Women's Health Initiative (WHI) trial results publicizing an increased risk of stroke, venous thrombosis, and breast cancer and no beneficial effect on coronary heart disease (CHD), use of CHT has declined, and there has been increased interest in alternative approaches. This review of the literature related to compounded BHT and the practices of its advocates is to determine if sufficient scientific evidence supports claims of greater efficacy and safety and any additional risks and uncertainties not generally associated with CHTs. Compounded BHTs have been promoted by some as natural, safer, and in some cases more efficacious than conventional hormone therapies, but there is a dearth of scientific evidence to support these claims. Compounded BHTs lack well controlled studies examining route of administration, pharmacokinetics, safety, and a critical, science-based rationale for the mixture and ratios of bioidentical estrogens employed in many preparations. Many advocates of compounded BHTs customize prescriptions based on saliva tests or blood sera levels in direct contradiction to evidence-based guidelines, which support tailoring HT individually according to symptoms. Currently, scientific uncertainties associated with compounded BHTs make their use less preferable to that of CHTs, as CHTs have been and continue to be assessed by clinical trials regarding both benefits and risks and are indicated for use according to evidence-based guidelines.