Understanding Women's Hormonal Health, Hormonal Changes & How Hormone Replacement Therapy Can Help
In the final installment of this three-part series, Matt and Kim Celmer explore the essential topic of hormonal health for women, highlighting its impact on both overt and silent symptoms of hormonal changes. Celmer offers practical advice for initiating meaningful conversations with healthcare providers about hormone levels with both diving into the intricacies of hormone replacement therapy (HRT)—what it is, how it works, and its potential benefits and risks. Addressing public concerns, they discuss the relationship between HRT and breast cancer, dosing considerations, and what care might look like for women seeking treatment. The episode concludes with thought-provoking questions and potential directions for future clinical research on hormones and health outcomes. For more information On Kim’s practice you can go to ICmedicine.com
Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!
https://pmc.ncbi.nlm.nih.gov/articles/PMC9178928/
Matt and Kim discuss the flaws with the interpretation of the women's health initiative study that suggested that hormone replacement therapy (HRT) predisposes women to cardiovascular and cancer disease risk. Namely, the misleading statistical analysis and the use of premerin (a synthetic progesterone analogue).
In contrast, Kim highlights the evidence suggesting HRT use prevents the incidence of disease in post menopausal women. This review presents the clinical trials highlighting the benefits of early administration of HRT for the prevention of cardiovascular disease, osteoporosis, and all-cause mortality in post-menopausal women.
https://pubmed.ncbi.nlm.nih.gov/24082040/
Matt and Kim discuss the importance of maintaining healthy testosterone levels in women, especially in regards to bone health and preventing osteoporotic fractures. This meta analysis demonstrates that oral contraceptive use is associated with a substantial reduction in total and free testosterone levels in several clinical trials in healthy women. Further, the lower free testosterone levels were accompanied by a higher level of sex hormone binding globulin (SHBG), which bind to testosterone and reduce its bioavailability. As osteoporosis is a major cause of morbidity in women, this data suggests that women using oral contraceptives should talk to their doctors about having their testosterone levels measured at baseline and post-contraceptive as a precaution.
Kim discusses data from Rebecca Glazer suggesting that testosterone does not increase cancer incidence and in fact may reduce the incidence/recurrence of breast cancer in certain contexts. Based on the physiology, it is likely that if testosterone plays any role in cancer progression, it’s when present at supra-physiological levels and it may fuel existing cancer cells rather than playing a causative role. This prospective cohort study was conducted on 1,268 women between the ages of 25-87 treated for symptoms of hormone deficiency and followed up for over 10 years. The participants were treated with subcutaneous testosterone prescribed on an individualized level. Breast cancer incidence was found to be 165 cases per 100,000 person years, significantly lower than the expected 271 cases per 100,000 person years, suggesting a protective effect from testosterone replacement therapy. These findings support the safety of subcutaneous testosterone therapy which can make a significant difference on the mental health, body composition, and quality of life of aging women.
A critique of the Women’s Health Initiative hormone therapy study - Fertility and Sterility
This study presents the flaws of the influential WHI hormone therapy study suggesting estrogen replacement therapy (including premarin) leads to increased risk of breast cancer. Criticisms include:
The study included women with an average age of 63, indicating treatment was conducted in older postmenopausal women. Earlier HRT administration following menopause has been demonstrated to be more effective
The study used premarin, a synthetic progesterone analogue, which has been demonstrated to exert cross-interactions with testosterone receptors, potentially influencing any adverse outcomes
Within the statistical analysis, the absolute incidence of breast cancer in treated and untreated cohorts was very small and results were not statistically significant.
These flaws with the WHI HRT study, combined with the data suggesting that estrogen replacement is beneficial for cardiovascular health, bone health, cognitive function, and quality of life in postmenopausal women, indicates that HRT may be an extremely important intervention strategy for healthy aging. Especially when dosing is personalized based on boosting estrogen levels to healthy/optimal ranges.
Kim highlights the complexities inherent within the data associating HRT with breast cancer in postmenopausal women by outlining evidence from a particular study suggesting that post-menopausal who received HRT had a higher incidence of breast cancer, but these tumors were easier to treat leading to better prognosis than women who did not receive HRT but developed breast cancer. This is the study Kim was referring to suggesting that HRT use was most strongly associated with an increased risk of invasive breast cancer presenting with a favorable prognosis. This suggests that while HRT may elevate the likelihood of developing breast cancer in some individuals/contexts, the cancers that do develop tend to be less aggressive and more responsive to treatment. This data further warrants research to understand the biological context and multi-faceted roles that HRT plays on healthy aging to inform better clinical decision making.
