Letter to the Editor: “Menopausal Hormone Therapy Is Associated With Reduced Total and Visceral Adiposity: The OsteoLaus Cohort”

The report by Papadakis et al. (1) that menopausal hormone therapy (MHT) is associated with significantly decreased visceral abdominal fat, body mass index, and android fat mass substantiates our clinical impressions of extended MHT and is consistent with our theory of euestrogenemia (2). There are at least 3600 estrogen signaling pathways ubiquitously distributed in the body. The theory of euestrogenemia postulates that estrogen is a hormone of homeostasis and that maintaining adequate estrogen levels for optimal estrogen receptor (ER) function is essential to health. That past users of MHT did not maintain the levels of visceral abdominal fat, body mass index, and android fat mass after cessation of MHT suggests ERs in those metabolic signaling pathways were downregulated and ceased to function.

Our patients live in the post-Women’s Health Initiative era of estrogen avoidance. Sarrel et al. (3) estimated there were 18,000 to 91,000 excess deaths in the United States in women aged 50 to 59 years from 2004 to 2009 because these women did not take MHT. We have proposed that this cohort suffered fatal metabolic consequences due to inadequate ER function in the presence of hypoestrogenemia (2, 4).

In an excellent review article, kinesiologists Spangenburg et al. (5) evaluated estradiol replacement vs exercise in ovariectomized (OVX) rodents to maintain proper metabolism. In OVX mice, access to voluntary running wheels did not protect against dysregulation in lipolytic function. However, supplementation with 17-β-estradiol was completely effective at preventing various changes of lipolytic dysregulation (5). There were also significant changes in key lipolytic signaling proteins that contribute to basal lipolytic rate. The authors showed decreases in levels of circulatory estrogens, leading to increased hepatic stearol coenzyme A desaturase-1 activity and proposed a two-hit hypothesis of visceral adipocyte dysfunction and increased hepatic stearol coenzyme A desaturase-1 content, making individuals more susceptible to nonalcoholic fatty liver disease. They stated that exogenous delivery of 17-β-estradiol can often prevent or reverse the metabolic dysfunction in the OVX and aromatase knockout mice, suggesting that estrogens are likely the critical regulator of metabolism and not another ovarian hormone (5).

The results seen in the current user cohort of OsteoLaus (1) add more data to favor the paradigm shift from the lowest dose or shortest duration of time of estrogen use for moderate to severe vasomotor symptoms and urogenital indications, to lifelong maintenance of physiologic euestrogenemia.

Acknowledgments

Disclosure Summary: R.J.T. is an instructor with Allied Health Media for Nexplanon. All honoraria are donated to the Foundation of the AAGL. I.J.K. has nothing to disclose.