Post-Menopause Hormone Imbalance and Cardiovascular Disease, with Erin Michos, MD, MHS

At the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, Erin Michos, MD, MHS, professor of medicine and Director of Women’s Cardiovascular Health at Johns Hopkins University School of Medicine, spoke on the impact of sex hormones on body composition changes in women throughout the lifespan, and how they may influence risk of cardiovascular disease (CVD) later in life.

CVD risk in women lags behind men by around 10 years, increasing steadily after the beginning of menopause. After menopause, the ovaries no longer produce estrogen sufficiently; the difference is made up by extraction from fat tissue, leading to obesity. Additionally, the postmenopausal ovaries contribute significantly to testosterone, which persists for ≥10 years after menopause.1

Given the sex differences in CVD risk factors, presentation, and outcomes, researchers have determined that hormones may have a direct role in the disease process. The combination of endogenous estrogen deficiency and relative excess of androgens like testosterone may be a critical cause of CVD risk.1

“In polycystic ovary syndrome [(PCOS)], the phenotype that’s associated with cardio-metabolic risk is the hyperandrogenous phenotype,” Michos told HCPLive. “With elevated androgen levels and with PCOS, there is this vicious cycle with increased abdominal fat in the visceral cavity that leads to further insulin resistance and hyperinsulinemia, and hyperinsulinemia can then increase androgen levels.”

Additionally, the decline in estrogen production during and after menopause can result in higher renin levels, increased production of vasoconstrictors like angiotensin II and endothelin-1, higher salt sensitivity, increased insulin resistance, and reduced vascular nitric oxide bioavailability. Each of these independently increases an individual’s risk for CVD.1

Michos explained that obesity cases in postmenopausal women are often a state of functional hyperandrogenism, given the dysregulation of sex hormones.

“Androgen [excess] can feed into visceral adiposity, visceral adiposity can feed into hyperinsulinemia, hyperinsulinemia can feed into hyperandrogenism, so it can be this vicious downward cycle,” Michos said. “It’s really important that we intervene on this for improvement in cardio-metabolic health.”

Use of androgens such as testosterone replacement therapy has also risen in some patient populations, reportedly for its libido-increasing effects. This treatment can further skew the hormonal balance towards androgenization. Estrogen replacement therapy, on the other hand, which is primarily taken to abate the symptoms of menopause, may benefit body composition.

“Estrogen therapy may have a favorable impact on body composition,” Michos said. “We do see a reduction in waist circumference and body fat in women who are getting estrogen therapy. However, I don’t recommend testosterone replacement therapy in women after menopause; that’s an off-label use of testosterone that some women have been using for libido effects.”

Looking forward, Michos stated that further research into reliable sex hormone assays is necessary.

“I think we need further studies about how to incorporate sex hormones, and particularly the importance of using reliable sex hormone assays,” Michos told HCPLive. “The field has gone to using mass spec as opposed to radio immunoassay.”

Michos reports the following disclosures: Astra Zeneca, Amgen, New Amsterdam, Merck, Novartis, Novo Nordisk, and others

References

1. Michos E. Sex Hormones and Anthropometric Measures & Heart Failure Risk in Women. Presented at the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.