Cardiometabolic Risk Factors and Endogenous Sex Hormones in Postmenopausal Women

A Cross-Sectional Study

Kristin Ottarsdottir; Åsa Tivesten; Ying Li; Ulf Lindblad; Margareta Hellgren; Claes Ohlsson; Bledar Daka

Disclosures

J Endo Soc. 2022;6(6) 

In This Article

Abstract and Introduction

Abstract

Context: It is uncertain which cardiovascular risk factors are associated with sex hormone levels in postmenopausal women.

Objective: This work aimed to investigate the association between cardiometabolic risk factors and sex hormones in a cross-sectional, observational population study.

Methods: In this Swedish population study, participants were physically examined from 2002 to 2004, and endogenous sex hormones were analyzed by liquid chromatography–tandem mass spectrometry. Women aged 55 years or older with estradiol levels below 20 pg/mL and not using any hormonal therapy were eligible for inclusion in the study (N = 146). Variable selection and bootstrap stability analyses were performed and linear regression models presented, with each of the 8 hormones as outcome variables.

Results: Body mass index (BMI) was positively associated with estradiol (β = 0.054, P < .001), but negatively associated with 17-α-hydroxyprogesterone (β = –0.023, P = .028). Waist-to-hip ratio (WHR) was negatively associated with dihydrotestosterone (β = –2.195, P = .002) and testosterone (β = –1.541, P = .004). The homeostatic model assessment of insulin resistance was positively associated with androstenedione (β = 0.071, P = .032), estradiol (β = 0.091, P = .009), estrone (β = 0.075, P = 0.009), and 17-α-hydroxyprogesterone (β = 0.157, P = .001). Age was positively associated with testosterone (β = 0.017, P = .042). C-reactive protein showed an inverse association with progesterone (β = –0.028, P = .037). Lower low-density lipoprotein cholesterol was associated with higher estradiol levels (β = –0.093, P = .049), whereas lower triglycerides were associated with higher concentrations of dihydrotestosterone (β = –0.208, P = .016).

Conclusion: In postmenopausal women, WHR was strongly inversely associated with androgens, while BMI was positively associated with estrogens.

Introduction

In addition to their fundamental role in reproduction physiology, sex hormones may be important for cardiovascular health.[1] Premenopausal women are less vulnerable to cardiovascular diseases than men, whereas the incidence of cardiovascular diseases in women increases markedly after the menopausal transition.[1,2] This may be a consequence of estrogen deficiency, leading to an increase in cardiovascular risk factors such as an adverse lipid profile,[3] weight gain and hypertension,[4] and endothelial dysfunction.[5,6] Nevertheless, higher endogenous estrogen levels in postmenopausal women are known risk indicators for developing insulin resistance,[7] breast cancer,[8] endometrial cancer,[9] and stroke.[10] On the other hand, higher estradiol levels in postmenopausal women have been associated with less adverse vascular remodeling both in the MSHeart Study[11] and in the Study of Women's Health Across the Nation Study (SWAN).[12] There is also evidence that different patterns of estrogen decline during the menopausal transition are associated with different levels of markers of atherosclerosis, such as the presence of carotid plaque.[13] Studies based on radioimmunoassay (RIA) measurements of sex hormone levels have shown a positive association between body mass index (BMI) and estrogen levels,[14–17] whereas there are contradictory findings regarding androgens. One observational study showed that waist circumference was positively associated with levels of androgens,[18] whereas other studies have found no association between waist-to-hip ratio (WHR) and testosterone.[19] Yet another study including both premenopausal and postmenopausal women (mean age, 47.5 years) found a negative association between visceral fat accumulation and dihydrotestosterone (DHT).[20] A review investigating 13 prospective studies found that all sex hormone levels were higher in obese postmenopausal women compared to lean postmenopausal women.[17]

RIA-based measurements are not suitable for the measurement of hormones in the lower range, that is, in postmenopausal women, children, or hypogonadal men, because of low precision and sensitivity.[21] Few population-based studies have used state-of-the art methods for sex steroid measurements in women, and there is a need for studies investigating how different variables are associated with endogenous sex hormones measured with more precise methods such as mass spectrometry.[21,22] Thus, the aim of this study was to investigate the association between risk factors for cardiovascular disease and 8 different sex hormones—17-α-hydroxyprogesterone, estrone, DHT, estradiol, dehydroepiandrosterone (DHEA), androstenedione, testosterone, and progesterone—measured with mass spectrometry in postmenopausal women.

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