Menopausal hormone therapy and risk of venous thromboembolism: The story so far.

Menopausal hormone therapy (MHT) is known to increase the risk of venous thromboembolism (VTE), which includes deep vein thrombosis, pulmonary embolism, and less frequently cerebral vein thrombosis, but the absolute risk for a given patient is very low. After starting MHT, the risk of VTE seems to be at its highest, declining to the non-HRT user baseline level of risk after stopping. Whether estrogen-only or estrogen-progestin HRT combination is linked to a similar risk of VTE is unclear from the available evidence. The aim of this study is to evaluate the risks of developing VTE in relation to different types as well as different modes of administration of MHT through a database search including PubMed, MEDLINE, Google Scholar, Cochrane Library, and others in order to provide the women carers with the up-to-date and evidence-based guidelines and recommendations while counseling the post-menopausal women enquiring on use of hormonal therapies either to alleviate the menopausal symptoms or to prevent the long-term sequelae of estrogen deficiency.

On sait que l'hormonothérapie ménopausique (MHT) augmente le risque de thromboembolie veineuse (TEV), qui comprend la thrombose veineuse profonde, l'embolie pulmonaire et, moins fréquemment, la thrombose veineuse cérébrale, mais le risque absolu pour un patient donné est très faible. Après le début du MHT, le risque de TEV semble être à son plus haut niveau, diminuant jusqu'au niveau de risque de base des non-utilisatrices de THS après l'arrêt. Les preuves disponibles ne permettent pas de savoir si un THS à base d'œstrogène seul ou d'association œstroprogestative est lié à un risque similaire de TEV. Le but de cette étude est d'évaluer les risques de développer une TEV par rapport à différents types ainsi qu'à différents modes d'administration du MHT grâce à une recherche dans des bases de données comprenant PubMed, MEDLINE, Google Scholar, Cochrane Library et autres afin de fournir aux femmes les soignants avec les lignes directrices et recommandations à jour et fondées sur des preuves tout en conseillant les femmes ménopausées qui se renseignent sur l'utilisation de thérapies hormonales, soit pour soulager les symptômes de la ménopause, soit pour prévenir les séquelles à long terme d'une carence en œstrogènes.

Hormone replacement therapy and breast cancer incidence in Korean women.

OBJECTIVES: After the 2002 Women's Health Initiative (WHI) study, the global use of menopausal hormone therapy (MHT) declined, and despite subsequent studies indicating a low risk of breast cancer, concerns about MHT usage persist. We examined the relationship between changes in MHT use and changes in the incidence of breast cancer from 2002 to 2020 in South Korea. STUDY DESIGN: This study used tumor registry information from 2002 to 2020 from the Korean Statistical Information Service and analyzed the incidence rate of invasive breast cancer in women, who were divided into two age groups: <50 and >50 years. The numbers of MHT prescriptions in Korea between 2002 and 2020 was determined from pharmacy data. RESULTS: The incidence of breast cancer per 100,000 women in South Korea increased from 34.3 in 2002 to 96.4 in 2020. Breast cancer incidence rates increased annually in both groups of women (those aged under and over 50 years), with no significant difference between the two (p = 0.614). Prescriptions for estrogen therapy (ET) in 2020 were 52.7 % lower than those in 2002. Prescriptions for estrogen-progesterone therapy (EPT) decreased by 27.9 % over the same period. Conversely, tibolone prescriptions, which had initially decreased by 25.4 % in 2004, subsequently showed a steady increase and were 93.6 % higher in 2020 than in 2002. CONCLUSION: The incidence of breast cancer increased annually in Korean women of all ages; however, the use of ET and EPT for MHT has declined since 2002, particularly the use of EPT after 2010. MHT, especially EPT, did not significantly increase the incidence of breast cancer in Korean women.

Menopausal hormone therapy and risk of sarcoidosis: a population-based nested case-control study in Sweden.

Sarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case-control study (2007-2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis. Dispensations of MHT were obtained from the Swedish Prescribed Drug Register before sarcoidosis diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression. Ever MHT use was associated with a 25% higher risk of sarcoidosis compared with never use (aOR 1.25, 95% CI 1.13-1.38). When MHT type and route of administration were considered together, systemic estrogen was associated with the highest risk of sarcoidosis (aOR 1.51, 95% CI 1.23-1.85), followed by local estrogen (aOR 1.25, 95% CI 1.11-1.42), while systemic estrogen-progestogen combined was associated with the lowest risk compared to never users (aOR 1.12, 95% CI 0.96-1.31). The aOR of sarcoidosis did not differ greatly by duration of MHT use. Our findings suggest that a history of MHT use is associated with increased risk of sarcoidosis, with women receiving estrogen administered systemically having the highest risk.

Cardiovascular health and the menopause, metabolic health.

Estrogen depletion following menopause predisposes to increased risk of cardiovascular disease (CVD), mainly due to ischemic heart disease. This is mostly evident in cases with premature menopause. The pathophysiological basis for this atherosclerotic process is the accumulation of several risk factors, such as abdominal obesity, atherogenic dyslipidemia, insulin resistance and arterial hypertension. The presence of vasomotor symptoms may further augment this risk, especially in women younger than 60 years. Menopausal hormone therapy (MHT) exerts many beneficial effects on lipid profile and glucose homeostasis as well as direct arterial effects, and may reduce CVD risk if initiated promptly (i.e.,<60 years or within ten years of the final menstrual period). Transdermal estradiol and micronized progesterone or dydrogesterone are the safest regimens in terms of venous thromboembolic events (VTE) and breast cancer risk. In any case, an individualized approach, taking into account the patient's total CVD, VTE and breast cancer risk, is recommended.

Cardiometabolic outcomes in Kronos Early Estrogen Prevention Study continuation: 14-year follow-up of a hormone therapy trial.

OBJECTIVE: This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS). METHODS: KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17ß-estradiol (Climara, 50 µg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years. KEEPS continuation recontacted KEEPS participants 14 years after randomization and 10 years after the completion of the 4-year clinical trial to attend in-person clinic visits. RESULTS: Participants of KEEPS continuation (n = 299 of the 727 KEEPS participants; 41%) had an average age of 67 years (range, 58-73 y). Measurements of systolic and diastolic blood pressures, waist-to-hip ratio, fasting levels of glucose, insulin, lipid profiles, and homeostasis model assessment of insulin resistance were not different among the treatment groups at either KEEPS baseline or at KEEPS continuation visits, or for change between these two visits. The frequency of self-reported diabetes ( P = 0.007) and use of diabetes medications was higher in the placebo than the oral conjugated equine estrogens ( P = 0.045) or transdermal 17ß-estradiol ( P = 0.02) groups, but these differences were not supported by the laboratory measurements of glycemia or insulin resistance. CONCLUSIONS: There was no evidence of cardiovascular and/or metabolic benefits or adverse effects associated with 4 years use of oral or transdermal forms of hormone therapy by recently menopausal women with good cardiovascular health after 10 years.

Use of MHT in women with cardiovascular disease: a systematic review and meta-analysis.

This systematic review assesses the effect of menopausal hormone therapy (MHT) on cardiovascular outcomes and risk factors in postmenopausal women with cardiovascular disease (CVD). The Medline, Embase and Cochrane databases were searched from inception to December 2022 for randomized controlled trials (RCTs) and observational studies using methodology from a previous Cochrane review. Quality assessment used the Cochrane risk of bias tool and Newcastle-Ottawa scale, respectively. From 5647 studies identified, 29 (23 RCTs and six observational studies) were included. Most studies were conducted in North America or Europe and investigated oral estrogens. Participants were older with varying frequency of cardiac risk factors and underlying CVD. No significant difference was observed between MHT users and controls regarding primary outcomes of non-fatal myocardial infarction, cardiovascular death or stroke. No difference in frequency of angina, heart failure and transient ischemic attacks was observed. Inconsistent effects of MHT on angiographic progression were seen and varied with glycemic status. Estradiol had a positive effect on flow-mediated dilatation. Limited studies identified differing effects of MHT on cardiac risk factors, varying with estrogen preparation. This study confirms no benefit of MHT for secondary CVD prevention, highlighting evidence limitations and the importance of shared decision-making when managing menopausal symptoms in women with CVD.

Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer.

Importance: Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer. Objective: To determine whether the risk of breast cancer-specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT). Design, Setting, and Participants: This cohort study analyzed 2 large cohorts, one each in Scotland and Wales, of females aged 40 to 79 years with newly diagnosed breast cancer. These population-based cohorts were identified from national cancer registry records from 2010 to 2017 in Scotland and from 2000 to 2016 in Wales and were followed up for breast cancer-specific mortality until 2020. Females were excluded if they had a previous cancer diagnosis (except nonmelanoma skin cancer). Data analysis was performed between August 2022 and August 2023. Exposure: Use of vaginal estrogen therapy, including vaginal tablets and creams, was ascertained from pharmacy dispensing records of the Prescribing Information System for the Scotland cohort and from general practice prescription records for the Wales cohort. Main Outcomes and Measures: The primary outcome was time to breast cancer-specific mortality, which was obtained from national mortality records. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for breast cancer-specific mortality, comparing vaginal estrogen therapy users with HRT nonusers and adjusting for confounders, including cancer stage and grade. Results: The 2 cohorts comprised 49 237 females with breast cancer (between 40 and 79 years of age) and 5795 breast cancer-specific deaths. Five percent of patients with breast cancer used vaginal estrogen therapy after breast cancer diagnosis. In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer-specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94). Conclusions and Relevance: Results of this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT. This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.

Progestogens for endometrial protection in combined menopausal hormone therapy: A systematic review.

Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen.

Beyond hot flashes: Exploring the role of estrogen therapy in postmenopausal women for myocardial infarction prevention and recovery.

Myocardial infarction (MI) commonly known as "heart attack" results from the blockage of blood flow to the heart. Postmenopausal women face an elevated risk of MI due to declining estrogen levels, a hormone pivotal in maintaining cardiovascular health. It promotes vasodilation, reduce inflammation, and improves lipid profiles. While estrogen therapy shows promise in mitigating MI risk for postmenopausal woman, its efficacy in prevention and recovery remains a subject of debate. This review provides a critical assessment of existing evidence on estrogen therapy's cardioprotective effects for postmenopausal women. It delves into estrogen's role in vascular function enhancement, inflammation reduction, and lipid metabolism modulation. Additionally, it addresses the various forms of estrogen therapy, administration methods, dosage considerations, safety implications, and associated risks. The review highlights the existing controversies and knowledge gaps related to estrogen therapy for MI prevention. It underscores the urgency for in-depth research to decipher the nexus between estrogen therapy and MI risk, especially concerning primary prevention and specific postmenopausal subgroups. Future studies should investigate optimal formulations, doses, and administration routes of estrogen therapy as well as assess treatment timing and duration. Comparative studies and long-term follow-up are necessary to inform clinical decision-making and improve patient care. Addressing these research gaps will empower clinicians to make more judicious choices about estrogen therapy for MI prevention and recovery in postmenopausal women, aiming for enhanced patient outcomes.

Breast cancer risk association with postmenopausal hormone therapy: Health Insurance Database in South Korea-based cohort study.

CONTEXT: Although many physicians have been concerned that the menopausal hormones used currently in clinical practice may affect the risk of breast cancer, there are currently few informative updated studies about the associations between menopausal hormone therapy (MHT) and the risk of breast cancer. OBJECTIVE: This study aims to evaluate the association between the risk of breast cancer and MHT using the National Health Insurance Database in South Korea (HISK) cohort between 2002 and 2019 retrospectively. METHODS: Postmenopausal women over 40 years of age from 2003 to 2011 were selected as the subject population, and their follow-up data were collected until 2019. We analyzed the risk and mortality of breast cancer according to the type of MHT received, namely, tibolone, combined estrogen plus progestin by manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by physician (CEPP), or topical estrogen. RESULTS: The risk of breast cancer increased in the CEPM group [hazard ratio (HR) 1.439, 95% CI 1.374-1.507, P-value < .001] in comparison with the non-MHT group. However, no significant associations were found between the use of tibolone, oral estrogen, CEPP, or topical estrogen and breast cancer risk in comparison with the non-MHT group (HR 0.968, 95% CI 0.925-1.012; HR 1.002, 95% CI 0.929-1.081; HR 0.929, 95% CI 0.75-1.15; HR 1.139, 95% CI 0.809-1.603). The mortality rate from breast cancer is lower in the MHT group in comparison with the non-MHT group, indicating that significant associations were found for tibolone, CEPM, and oral estrogen (HR 0.504, 95% CI 0.432-0.588; HR 0.429, 95% CI 0.352-0.522; HR 0.453 95% CI 0.349-0.588, P-value < .001). CONCLUSIONS: This study suggests that the risk of breast cancer is increased by drugs in the CEPM group but not by tibolone, oral estrogen, CEPP, or topical estrogen. The mortality rate from breast cancer is lower with MHT (tibolone, CEPM, oral estrogen) than without MHT.

Dementia in Women Using Estrogen-Only Therapy.

This study examines the association between use of estrogen-only therapy for perimenopausal and menopausal women and risk of dementia.

Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study.

OBJECTIVE: To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer. DESIGN: A retrospective cohort study. PATIENTS OR OTHER PARTICIPANTS: Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019. INTERVENTIONS: Participants were divided into MHT and non-MHT groups; the MHT group was analyzed in detail by dividing participants into tibolone, combined estrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), oral estrogen alone, and topical estrogen subgroups. MAIN OUTCOME MEASURES: The incidence of gallstones and gallbladder cancer was compared between the two groups. RESULTS: This study enrolled 1,004,034 and 381,711 patients in the non-MHT and the MHT groups, respectively. The incidence of gallstones was 2.6% in the non-MHT group and 3.4%, 2.6%, 3.4%, 3.2%, and 4.4% in the tibolone, CEPM, oral estrogen alone, CEPP, and topical estrogen groups, respectively. Cox proportional hazard analysis revealed that all hormones increased the risk of gallstones ([tibolone] hazard ratio [HR]: 1.347, 95% confidence interval [CI]: 1.309-1.387, [CEPM] HR: 1.146, 95% CI: 1.1-1.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18-1.305, [CEPP] HR: 1.164, 95% CI: 1.01-1.341, [topical estrogen] HR: 1.602, 95% CI: 1.295-1.983). However, the risk of gallbladder cancer did not change with any hormone therapy. CONCLUSIONS: All types of MHT including tibolone, increased the risk of gallstones. This risk was the highest with topical estrogen, which may be a result of selection bias due to concerns regarding the adverse effects of CEE and MPA.

Menopausal hormone therapy and central nervous system tumors: Danish nested case-control study.

BACKGROUND: Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently. METHODS AND FINDINGS: Nested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur. CONCLUSIONS: Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.

[Russian eligibility criteria prescribing menopausal hormonal hormones therapy for patients with cardiovascular and metabolic diseases. Consensus document of the Russian Cardiological Society, Russian Society of Obstetricians and Gynecologists, Russian Association of Endocrinologists, Eurasian Association of Therapists, Association of Phlebologists of Russia].

Menopausal symptoms can disrupt the life course of women at the peak of their career and family life. Currently, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormonal therapy is the fear of doctors who are afraid of doing more harm to patients than good. Caution is especially important when it comes to women with underlying health conditions. Moreover, it should be recognized that there is a lack of high-quality research regarding the safety of MHT for major chronic non-infectious diseases and common comorbid conditions. The presented consensus document analyzed all currently available data obtained from clinical trials of various designs and created a set of criteria for the acceptability of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, doctors of various specialties who advise women in menopause will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real practice.

Association Between Menopausal Hormone Therapy and Risk for Parkinson's Disease.

BACKGROUND: The relationship between menopausal hormone therapy (MHT) and risk of Parkinson's disease (PD) remains controversial. OBJECTIVE: This nationwide population-based cohort study investigated the association between MHT and PD development. METHODS: Data from the National Health Insurance System of South Korea from 2007 to 2020 were used. The MHT group included women who underwent MHT for the first time between 2011-2014, while the non-MHT group included women who visited a healthcare provider for menopause during the same period but never received hormonal therapy. We used propensity score matching (1 : 1) to adjust for potential confounders, and Cox regression models to assess the association between MHT and PD. RESULTS: We selected 303,260 female participants (n = 151,630 per MHT and non-MHT groups). The median age of the participants was 50 (48-54) years, and the follow-up period lasted 7.9 (6.9-8.9) years. Cox regression analysis revealed an increased risk of PD with MHT (hazard ratio [HR] 1.377, 95% confidence interval [CI] 1.184-1.602), particularly with tibolone (HR 1.554, 95% CI 1.297-1.861) and estrogen alone (HR 1.465, 95% CI 1.054-2.036). Tibolone and estrogen alone were linked to PD within three years; however, no association was observed after three years. In contrast, the use of combined estrogen-progesterone was linked to a higher risk of PD, which increased with the duration of MHT (HR 1.885, 95% CI 1.218-2.918 for over five years). CONCLUSIONS: This study demonstrated that the MHT is closely associated with the risk of PD in a regimen- and duration-specific manner.

'Tis but a scratch: a critical review of the Women's Health Initiative evidence associating menopausal hormone therapy with the risk of breast cancer.

ABSTRACT: Use of menopausal hormone therapy (HT) fell precipitously after 2002, largely as a result of the Women's Health Initiative's report claiming that the combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased breast cancer risk and did not improve quality of life. More recently, Women's Health Initiative (WHI) publications acknowledge HT as the most effective treatment for managing menopausal vasomotor symptoms and report that CEE alone reduces the risk of breast cancer by 23% while reducing breast cancer death by 40%. Their sole remaining concern is a small increase in breast cancer incidence with CEE and medroxyprogesterone acetate (1 per 1,000 women per year) but with no increased risk of breast cancer mortality. This article closely examines evidence that calls even this claim of breast cancer risk into serious question, including the WHI's reporting of nonsignificant results as if they were meaningful, a misinterpretation of its own data, and the misleading assertion that the WHI's findings have reduced the incidence of breast cancer in the United States. A generation of women has been deprived of HT largely as a result of this widely publicized misinterpretation of the data. This article attempts to rectify this misunderstanding, with the goal of helping patients and physicians make informed joint decisions about the use of HT.

Compounded Bioidentical Menopausal Hormone Therapy: ACOG Clinical Consensus No. 6.

SUMMARY: Many compounding pharmacies use the phrase "bioidentical hormone" as a marketing term to imply that these preparations are natural and, thus, safer and more effective than U.S. Food and Drug Administration (FDA)-approved menopausal medications that use bioidentical or synthetic hormones or both. However, evidence to support marketing claims of safety and effectiveness is lacking. Compounded bioidentical menopausal hormone therapy should not be prescribed routinely when FDA-approved formulations exist. Clinicians should counsel patients that FDA-approved menopausal hormone therapies are recommended for the management of menopausal symptoms over compounded bioidentical menopausal hormone therapy. If a patient requests the use of compounded bioidentical menopausal hormone therapy, clinicians should educate them on the lack of FDA approval of these preparations and their potential risks and benefits, including the risks specific to compounding. To truly understand the benefits and harms of compounded bioidentical menopausal hormone therapy, high quality placebo-controlled randomized controlled trials with long-term follow-up comparing custom-compounded products with FDA-approved menopausal hormone therapy are needed.