Bioidentical Research Articles

Prescribing Bioidentical Menopausal Hormone Therapy: A Survey of Physician Views and Practices.

It is estimated that 1-2.5 million U.S. women use compounded bioidentical menopausal hormone therapy (MHT). However, the proportion of American physicians prescribing compounded bioidentical hormones remains unknown. This study aims to evaluate obstetrician-gynecologists' (OB/GYNs) and family medicine physicians' decisions reflected in prescribing practices of MHT in Kansas, and level of agreement with the American College of Obstetricians and Gynecologists (ACOG) recommendations. An Internet-based 38-item survey was electronically disseminated to OB/GYNs and family medicine physicians identified through the Kansas State Board of Healing Arts licensure list. Out of 1349 physicians contacted, 164 (12.2%) responded to the survey. There were 128 (9.5%) responses included in the final analysis. In the past year, 96.1% (123/128) of respondents prescribed conventional MHT, 93.0% (119/128) prescribed Food and Drug Administration (FDA)-approved bioidentical MHT, and 66.1% (84/127) prescribed compounded bioidentical MHT. Of factors influencing MHT-prescribing practices, FDA regulation was not important to 16.7% (21/126) of physicians, whereas customization was important to 68.5% (87/127). There was a significant difference between specialties, 37.7% of OB/GYNs compared with 56.9% of family medicine physicians, regarding the ACOG statement that "patients should be counseled that conventional MHT is more appropriate than compounded preparations" (p = 0.031). Respondents disagreed with ACOG regarding the statements that "the practice of compounding makes it difficult to identify the active agent responsible for various effects" (41.0% of OB/GYNs and 34.8% of family medicine physicians) and "the practice of custom blending commercially available drug products lacks both a strong biological rationale and medical evidence for effectiveness" (36.1% of OB/GYNs and 37.9% of family medicine physicians). Prescribing practices for MHT vary between specialties. This study identifies a meaningful level of disagreement with ACOG recommendations regarding prescription of compounded rather than FDA-approved MHT. Further research is needed to better understand this level of discordance.

Compounded Bioidentical Hormone Therapy

Compounded Bioidentical Hormone Therapy

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.

Promotion and marketing of bioidentical hormone therapy on the internet: a content analysis of websites.

To evaluate the quality of information presented and claims made on websites offering bioidentical hormone therapy (BHT) products or services. A quantitative content analysis was completed on 100 websites promoting or offering BHT products or services. Websites were identified through Google search engine from September to October 2013. Search terms included "bioidentical hormone therapy" or "bioidentical progesterone," accompanied by "purchase or buy," "service," or "doctors." The Brief DISCERN instrument was used to determine the quality of the health information. Websites were from Canada (59%), United States (38%), and other countries (3%). Almost half of the websites originated from medical clinics (47%), and healthcare professionals offering BHT services included physicians (50%), pharmacists (19%), and naturopaths (16%). Majority of websites promoted BHT as custom-compounded formulations (62%), with only 27% indicating that BHT is also commercially available. Websites overall claimed that BHT had less risk compared with conventional hormone therapy (62%). BHT was described as having less breast cancer risk (40%), whereas over a quarter of websites described BHT as "protective" for breast cancer. Websites mainly targeted women (99%), with males mentioned in 62% of websites. Product descriptors used to promote BHT included individualization (77%), natural (70%), hormone imbalance (56%), and antiaging (50%). The mean Brief DISCERN score was 15, indicating lower quality of information. Claims made about BHT on the internet are misleading and not consistent with current professional organizations' recommendations. Understanding how BHT may be promoted on the internet can help healthcare professionals when educating patients.

BMS statement on custom-compounded 'bioidentical hormones'.

BMS statement on custom-compounded 'bioidentical hormones'.

American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on Menopause–2017 Update

the use of menopausal hormone therapy in symptomatic postmenopausal women should be based on consideration of all risk factors for cardiovascular disease, age, and time from menopause. 2. the use of transdermal as compared with oral estrogen preparations may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease. 3. when the use of progesterone is necessary, micronized progesterone is considered the safer alternative. 4. in symptomatic menopausal women who are at significant risk from the use of hormone replacement therapy, the use of selective serotonin re-uptake inhibitors and possibly other nonhormonal agents may offer significant symptom relief. 5. AACE does not recommend use of bioidentical hormone therapy. 6. AACE fully supports the recommendations of the Comité de l'Évolution des Pratiques en Oncologie regarding the management of menopause in women with breast cancer. 7. HRT is not recommended for the prevention of diabetes. 8. In women with previously diagnosed diabetes, the use of HRT should be individualized, taking in to account age, metabolic, and cardiovascular risk factors. AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CAC = coronary artery calcification; CEE = conjugated equine estrogen; CEPO = Comité de l'Évolution des Pratiques en Oncologie; CAD = coronary artery disease; CIMT = carotid intima media thickness; CVD = cardiovascular disease; FDA = Food and Drug Administration; HDL = high-density lipoprotein; HRT = hormone replacement therapy; HT = hypertension; KEEPS = Kronos Early Estrogen Prevention Study; LDL = low-density lipoprotein; MBS = metabolic syndrome; MPA = medroxyprogesterone acetate; RR = relative risk; SERM = selective estrogen-receptor modulator; SSRI = selective serotonin re-uptake inhibitor; VTE = venous thrombo-embolism; WHI = Women's Health Initiative.

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.

The effect on quality of life via bio-mimetic hormone replacement therapy for breast cancer patients.

113 Background: Many treatments for breast cancer block the estrogen receptors to reduce the risk of relapse. However, this treatment results in massive changes to the normal hormonal milieu. When the normal rhythmic hormonal patterns are disrupted, either through treatment or normal menopause, women typically experience a multitude of harsh symptoms with little affect on relapse rate. We set out to examine and evaluate the effects of estrogen (E2) and progesterone (P4) treatments via a bio-mimetic bio-identical hormone replacement therapy (BBHRT). We theorized, through the analysis of physiological and clinical literature, that the use BBHRT in the normal physiological pattern of reproductive women will lead to an increase of overall well-being and better quality of life for post-treatment and menopausal women, but does not increase their risk of breast cancer. Methods: E2 and P4 control over 9,000 different gene products and a disruption of these processes can lead to an increase in illnesses of aging including cancer. Through an evaluation of current literature, we theorize that a BBHRT approach utilizing E2 and P4 in a bio-mimetic manner to restore a woman’s body to normal hormonal levels can be achieved through twice-daily transdermal applications of hormonal creams with peaks in serum levels on days 12 and 21. The proposed method uses compounded, bio-identical hormones dosed to mimic the female reproductive cycle. Results: While this is a proposed clinical study, it is expected that women will experience resolution of menopausal and post-treatment symptoms, including better sleep, decreased migraines and incontinence, increased focus, and increased libido. By restoring the normal hormonal rhythm, it is anticipated that the body’s natural response elements will help restore both quality of life and well being, while also protecting from possible relapse. Conclusions: We propose a method to provide better quality of life and well being for women through BHRT that combines the use of E2 and P4 in a manner that mimics a woman’s normal reproductive levels. While a small long-term study of this method has shown promising results, we conclude that further, most detailed studies are still needed.

Brain nutrition, aging and neuroplasticity: The clinical orthomolecular aspects

The state-of-the-art advances in neuroscience and anti-aging medicine show that the brain can adapt to chronic stress by increasing its neuroplasticity capacity. Neuroplasticity allows the neurons in the brain to compensate for injury and disease and to adjust their activities in response to new situations or to changes in their environment. The aging brain can adapt through cellular defense mechanisms, such as DNA repair, release of neurotrophins (BDNF, IGF-1), and promotion of neurogenesis, and also through the capability of the dendrites and synapses to change in response of the environmental demands, including nutrition. The brain’s perfect immunity regulation by the microglia and the central nervous system’s antioxidant capacity enhancement depends on several concepts, including the best nutritional foods and supplements, hormones, physical activity and learning procedures. The orthomolecular medicine establishes the use of the correct molecules to keep the perfect physiological and biochemical function of the body. The aim of this talk is to reveal the biochemical and immunological mechanisms behind the brain aging and to address the best clinical orthomolecular protocols to prevent the neurodegenerative diseases and stimulate the neuroplasticity with the use of dietary substances, natural immune-modulatory molecules and bioidentical hormones.

Bioidentical Estrogen for Menopausal Depressive Symptoms: A Systematic Review and Meta-Analysis.

Proponents of bioidentical estrogens claim that they are superior for treating menopausal symptoms, including depressive symptoms. Small trials examining the effects of bioidentical estrogens on depressive symptoms show conflicting results. We conducted a systematic review to assess the effectiveness and safety of bioidentical estrogens for treatment of depressive symptoms in peri- and postmenopausal women. We searched the scientific literature for randomized controlled trials of at least 4 weeks duration, comparing bioidentical estrogen with placebo for depressive symptoms in menopausal women. The main outcome measure was improvement in depressive symptoms on a validated scale. We found 12 clinical trials that met inclusion criteria, two of which contained insufficient data for quantitative analysis. In the 10 studies (inclusive of 1208 subjects) for which complete data were available for inclusion in the meta-analysis, bioidentical estrogen had no clinically significant effect on depressive symptoms (standardized mean difference [SMD] -0.02; confidence interval [95% CI] -0.41 to +0.38). Pooled studies were highly heterogeneous, and numerous approaches to reducing heterogeneity were unsuccessful. Subgroup analyses showed no significant difference in effect for women treated with adjunctive progestogen, women treated with unopposed estrogen, perimenopausal, or postmenopausal and mixed populations. A possible benefit in perimenopausal women treated with unopposed estradiol may have been diluted by studies including older postmenopausal women whose depressive symptoms were unrelated to menopause. In this first systematic review of bioidentical hormone replacement therapy, we found that bioidentical estrogen has no clear benefit in treating depressive symptoms in menopausal women, but heterogeneity of available studies limits the potential for definitive conclusions. Future research should compare bioidentical estrogen with nonbioidentical estrogen for treatment of depressive symptoms in perimenopausal women.

Bioidentical hormone therapy: An assessment of provider knowledge

ObjectivesBioidentical hormone therapy (BHT) is available in the United States in formulations that have been approved by the Food and Drug Administration (FDA) but also in formulations that have not been so approved. The aim of this study was to evaluate the knowledge, beliefs, and prescribing practices of BHT among healthcare providers. Study designA cross-sectional self-selected responder survey was conducted of health care providers attending primary care Continuing Medical Education (CME) conferences in the United States from May 2012 to April 2013. The questionnaire consisted of 26 items assessing knowledge, beliefs, and current practice around BHT. ResultsA total of 366 survey responses were analyzed. Though 69.8% of respondents accurately identified the definition of BHT, only 45.3% were aware that BHT is available in FDA-approved products and 34.2% of respondents incorrectly identified that BHT is available only in custom-compounded formulations. Of those who had prescribed CC-BHT, less than half agreed with the statement “I am comfortable prescribing BHT” (45.4%). ConclusionsOur study showed that many practitioners are unaware that bioidentical hormones are available in FDA-approved products. Knowledge gaps identified by this survey highlight the need for and importance of education to further dispel misinformation surrounding the topic.

Bioidentical hormones for women with vasomotor symptoms.

Bioidentical hormones for women with vasomotor symptoms.

A Word About Bioidenticals

A Word About Bioidenticals

Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement.

This Scientific Statement finds that there is no rationale for routine prescribing of unregulated, untested, and potentially harmful custom compounded bioidentical hormone therapies.

Use of Menopausal Hormone Therapy and Bioidentical Hormone Therapy in Australian Women 50 to 69 Years of Age: Results from a National, Cross-Sectional Study.

Menopausal Hormone Therapy (MHT) use in Australia fell by 55% from 2001 to 2005, following the release of large-scale findings on its risks and benefits. Comprehensive national data, including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004–5 National Health Survey, when 11% of women aged 45+ years were estimated to be current MHT users. No national data are available on prevalence of use of “bioidentical” hormone therapy (BHT). The objective of this study was to determine recent prevalence of MHT and BHT use. A cross-sectional, national, age-stratified, population survey was conducted in 2013. Eligible women, aged 50–69 years, resident in Australia were randomly sampled in 5-year age groups from the Medicare enrolment database (Australia’s universal health scheme). The response rate was 22% based on return of completed questionnaires, and analyses were restricted to 4,389 women within the specified age range. The estimated population-weighted prevalence of current use of MHT was 13% (95%CI 12–14), which was broadly similar to the previously reported national figures in 2004–5, suggesting that the use of MHT in Australia has largely stabilised over the past decade. A total of 39% and 20% of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT, respectively, whereas 77% of hysterectomised current-users used oestrogen-only MHT. Almost three-quarters of current-users [population-weighted prevalence 9% (95%CI 8–10)] had used MHT for ≥5 years. In regard to BHT, estimated population-weighted prevalence of ever use was 6% (95%CI 6–7) and 2% (95%CI 2–3) for current use. The population-weighted prevalence of MHT and BHT combined, in current users in their fifties and sixties was 15% (95%CI 14–16). These data provide a recent national “snapshot” of Australian women’s use of both conventional MHT and of BHT.

Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial.

To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms. A randomized, single blind, four arm, parallel assignment study was conducted in VMMC and SJH, New Delhi, India. 200 Indian menopausal women were recruited and assigned into four treatment groups viz., estradiol valerate (E2V), conjugated equine estrogen (CEE), isoflavones and Placebo group. The statistical significance of categorical variables was determined by Chi-square, Fisher's exact test. In case of quantitative variable parametric test Student's t test was used. In case of quantitative variables where data are not normally distributed, Kruskal-wallis test and Wilcoxon Mann-Whitney test were used. Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups. Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes. 91.9% decrease was observed in mean hot flash score in the E2V group after 24weeks of treatment, 89.2% in the CEE group, 60.42% decrease in the isoflavones group. While placebo led to 47.9% decrease in mean hot flash score. After 24weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group. No serious side effect was reported in any of the groups. Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24weeks. However, it seems more reasonable to replenish with less costly and bio-identical hormone, i.e. micronized estradiol valerate which is equally effective. The trial was registered under Clinical trial registry of India prospectively (number: CTRI/2012/04/002566).

Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy.

Objective:We review the historical regulation of drug compounding, concerns about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded bioidentical hormone therapies (CBHTs), which do not have proper labeling and warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA) on compounding.Methods:US government websites were searched for documents concerning drug compounding regulation and oversight from 1938 (passage of Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including chronologies, Congressional testimony, FDA guidelines and enforcements, and reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for articles on compounded drugs, including CBHT.Results:Congress explicitly granted the FDA limited oversight of compounded drugs in a 1997 amendment to the FDCA, but the FDA has encountered obstacles in exercising that authority. After 64 patient deaths and 750 adversely affected patients from the 2012 meningitis outbreak due to contaminated compounded steroid injections, Congress passed the DQSA, authorizing the FDA to create a voluntary registration for facilities that manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA regulations for traditional compounding. Given history and current environment, concerns remain about CBHT product regulation and their lack of safety and efficacy data.Conclusions:The DQSA and its reinforcement of §503A of the FDCA solidifies FDA authority to enforce FDCA provisions against compounders of CBHT. The new law may improve compliance and accreditation by the compounding industry; support state and FDA oversight; and prevent the distribution of misbranded, adulterated, or inconsistently compounded medications, and false and misleading claims, thus reducing public health risk.

Update on primary ovarian insufficiency.

Despite an incidence of 1% among women under the age of 40, primary ovarian insufficiency (POI) is still poorly understood. As the variable cause and presentation of POI complicate its management, a standard regimen for treatment remains to be established. However, emerging research has provided new insight on current mainstays of treatment as well as novel management approaches and therapeutic interventions. Recent clinical trials in women with POI indicate that the widely used regimen of transdermal estradiol and medroxyprogesterone acetate restores bone mineral density to a level equal to women with normal ovarian function. Further research verifies that compounded bioidentical hormones and androgen supplementation are inadequate in treating POI and lowering risk for long-term sequelae. Additionally, assessing changes in bone turnover markers may be useful for monitoring bone mineral density. Alternative therapies such as acupuncture, dehydroepiandrosterone, and bupropion may be effective in treating the effects of estrogen deficiency at some level, but require further investigation. Recent updates show promise in improving management methods and reducing risk of long-term sequelae. Additional research that expands upon the most current literature is critical to achieve an evidence-based standard of best practice.

A new solubilized vaginal estradiol in a VagiCap™ for the treatment of vaginal atrophy

approved by regulatory agencies worldwide for these indications. The use of HT has declined during the past 12 years in response to the Women’s Health Initiative (WHI) trials. Paradoxically, the use of non-FDAapproved compoundedhormone therapy (CHT) has increased. Recent studies reported that up to 2.5millionUSwomen use non-FDA approved compounded HT containing 17 -estradiol and progesterone annually [1]. The use of compounded HT in the European Union (EU) is not well characterized but is also likely increasing. Non FDA-approved compounded 17 -estradiol and progesterone are often used in varying combinations without the benefit of adequate testing for safety, efficacy and quality of manufacturing. This is a public health issue of great proportion and is often occurringwithout the recognitionofhealth careproviders and their patients as many of them lack knowledge about the differences in testing and oversight of FDA approved and regulated products versus compounded products [1,2]. Up to now, no single product combining natural 17 -estradiol and progesterone has been approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The phase 3 REPLENISH trial is underway to study a novel oral formulation of solubilized 17 -estradiol and natural progesterone combined in a single softgel capsule (TX-001HR; TherapeuticsMD) for treating vasomotor symptoms (VMS) in postmenopausal women. The REPLENISH trial evaluates the efficacy and safety of 4 doses of TX-001HR versus placebo for the reduction of moderate to severeVMS frequency and severity at 4 and12weeks andevaluates the endometrial safety of the combinations at 1 year. TX-001HR contains hormones that are molecularly identical to endogenous estradiol and progesterone and is intended as an option for women who prefer bioidentical hormones; further, it does not contain peanut oil, a common allergen. Published data suggest a safer profile of estradiol and natural progesterone compared with HT containing conjugated equine estrogens and progestins [3]. The type of progestogen included in HT may influence the incidence of breast cancer [4]. Observational studies have reported that oral estrogens natural and progesterone has no effect on increasing breast cancer risk as opposed to oral estrogens combined with various progestins [4].

How Common Is Compounded Hormone Therapy for Menopause Symptoms

Although use of hormone therapy (HT) for menopause symptoms has declined in recent years, use of compounded hormone therapy (CHT; also called bioidentical hormone therapy) use seems to have risen, perhaps fueled by celebrity endorsements, unregulated advertising, and beliefs about the safety of “natural” hormones. CHT is not FDA-regulated and its prescriptions not tracked; therefore, use rates are difficult to know. Investigators estimated …