BHRT Abstracts 5

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Virilisation in siblings secondary to transdermal 'bioidentical' testosterone exposure.
            (Huynh and Stewart, 2017) Download
We present cases of siblings with virilisation from transder- mal exposure to ‘bioidentical’ testosterone (bioT).

Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal.
            (L'Hermite, 2017b) Download
The many advantages of registered bioidentical sex hormones over registered, conventional, non-bioidentical menopausal hormone therapy (MHT) are considered. The transdermal route of estrogen administration avoids excess venous thromboembolic and ischemic stroke events. There is some indication that conjugated equine estrogens are more thrombogenic and most likely induce some hypertensive responses; estradiol might also be superior to conjugated equine estrogens (CEE) in terms of global cardiovascular health. The most valid evidence presently suggests that CEE-only treatment does not increase the risk of breast cancer and even may reduce it. But its combination with a synthetic progestogen (mainly medroxyprogesterone acetate) is a critical issue since it seems to be primarily associated with an increased incidence of breast cancer, however similar to or lower than that associated with some common lifestyle factors. Though not yet proven in a randomized, controlled trial, MHT continuously combining oral micronized progesterone with transdermal estradiol can presently be considered as the optimal MHT. It is not only safer than custom-compounded bioidentical hormones but also than oral conventional MHT and has the best breast profile; registered products for such optimal MHT are available around the world and must be preferred.


 

Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use.
            (L'Hermite, 2017a) Download
Wide rejection of conventional hormone therapy (HT) after the initial publication of the Women's Health Initiative (WHI) led to unjustified use of custom-compounded bioidentical hormones. In the USA, it became an unregulated drug manufacturer industry in disguise, without proper control and making false claims and misleading advertisements. Manufacturing quality is not ensured. Unspecific harm from compounding has occurred on a large scale, such as deaths from infected products and end-stage renal failure plus carcinoma due to confusion between different Chinese herbs. Oral estrogens increase venous thromboembolic and ischemic stroke events, even more when overdosed; these excess risks can be avoided by non-oral administration, readily accessible in custom-compounded HT by administering estradiol through diverse routes (of which transdermal is the best documented). Another risk specific to custom-compounded HT, resulting from estrogen/progestogen imbalance, might be excess endometrial carcinomas. HT can be optimized by continuously combining transdermal estradiol with progesterone (when required). Registered preparations do exist for such a more physiological treatment and therefore must be preferred. Custom compounding is only seldom legitimate, for example in case of allergy (such as to peanut oil) or to prescribe different combinations, doses or components (e.g. estriol, dehydroepiandrosterone or testosterone), even when not approved by local regulatory authorities despite being scientifically acceptable.

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.
            (Velentzis et al., 2016) Download
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.

Bioidentical Estrogen for Menopausal Depressive Symptoms: A Systematic Review and Meta-Analysis.
            (Whedon et al., 2017) Download
BACKGROUND:  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. METHODS:  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. RESULTS:  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. CONCLUSIONS:  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.


 

References

Huynh, T and CI Stewart (2017), ‘Virilisation in siblings secondary to transdermal ‘bioidentical’ testosterone exposure.’, J Paediatr Child Health, 53 (3), 301-5. PubMed: 28070908
L’Hermite, M (2017a), ‘Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use.’, Climacteric, 20 (3), 205-11. PubMed: 28509626
——— (2017b), ‘Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal.’, Climacteric, 1-8. PubMed: 28301216
Velentzis, LS, et al. (2016), ‘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.’, PLoS One, 11 (3), e0146494. PubMed: 27008039
Whedon, JM, et al. (2017), ‘Bioidentical Estrogen for Menopausal Depressive Symptoms: A Systematic Review and Meta-Analysis.’, J Womens Health (Larchmt), 26 (1), 18-28. PubMed: 27603786