Functional Hypothalamic Amenorrhea Phenotype and Cardiovascular Disease Risk.

Authors

Chrisandra L Shufelt, Jennifer J Stuart, Jana Karam, Xiaoyu Che, JoAnn E Manson, Karen K Miller, Kathy Rexrode, Stephanie Faubion, Sarah Berga, C Noel Bairey Merz, Janet W Rich-Edwards

Published in

The Journal of clinical endocrinology and metabolism. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Menstrual irregularities have been associated with cardiovascular disease (CVD) risk, but underlying etiologies may confer distinct risk profiles. Functional hypothalamic amenorrhea (FHA) has not been evaluated as a separate risk phenotype.
To assess the association between FHA phenotype and incident CVD and cardiometabolic risk factors.
Prospective cohort study with biennial follow-up from 1993 to 2019.
Nurses' Health Study II cohort.
The sample included 52,655 premenopausal women free of CVD in 1993. FHA phenotype was defined as irregular or absent cycles without PCOS traits combined with low body mass index and/or high physical activity.
None.
Incident CVD (coronary heart disease [CHD; myocardial infarction or coronary revascularization] and stroke) and incident elevated cholesterol, hypertension, and type 2 diabetes (T2DM).
During up to 26 years of follow-up, 1,007 CVD events occurred. Among women who developed CVD, the median time to the first CVD event was 17.0 years (IQR, 11.3-21.0). FHA phenotype in mid-adulthood was associated with a 62% higher risk of CVD (95% confidence interval [CI]: 1.01-2.59), driven by an almost two-fold higher risk of CHD (hazard ratio [HR] = 1.91; 95% CI: 1.11-3.27), compared with women with regular cycles. FHA was also associated with T2DM (HR = 1.86; 95% CI: 1.41-2.47), but not hypertension or elevated cholesterol. Non-FHA menstrual irregularity was associated with elevated cholesterol, hypertension, and T2DM, but not CVD. FHA in early adulthood was not associated with outcomes.
FHA phenotype in mid-adulthood was associated with increased CHD risk independent of traditional risk factors. Menstrual history may serve as an early marker of cardiometabolic risk.

PMID:
42831273
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.