Elevated Production and Metabolic Clearance Rates of Androgens in Morbidly Obese Women

Abstract

Blood production rates of testosterone, dihydrotestosterone (DHT), and 3 alpha-androstanediol (3 alpha-diol) were found to be approximately 2-fold elevated in morbidly obese, nonhirsute, normally menstruating women. Values were intermediate between those found in normal women and those in a group of nonobese normally menstruating women with idiopathic hirsutism. Elevated androgen production rates in obese women were associated with 2- to 3-fold increases in MCRs, presumably due to decreased levels of sex hormone-binding globulin. Thus, increased production rates were offset by increased MCRs, resulting in plasma testosterone, DHT, and 3 alpha-diol concentrations that were similar in the obese and normal women. By contrast, women with hirsutism had increased production rates associated with elevated plasma androgens as well as increased MCRs. Urinary excretion of testosterone glucuronide and 3 alpha-diol glucuronide (3 alpha-diol G) were elevated in both obese and hirsute women, paralleling the increased androgen production rates. Despite increased production rates and excretion of androgens, obese women exhibited no menstrual abnormalities, hirsutism, or other signs of virilism. To explore the apparent ineffectiveness of increased androgen production to produce virilizing symptoms, we measured plasma 3 alpha-diol G levels as a measure of peripheral androgen action. The mean +/- SE plasma 3 alpha-diol G was 53 +/- 8 ng/dl in obese women and 36 +/- 6 in normal women; by contrast, women with idiopathic hirsutism had levels of 440 +/- 99, a 12-fold elevation. Plasma testosterone glucuronide in obese and hirsute women were only 2- to 3-fold elevated, while plasma DHT glucuronide was not increased in obese women and was only 2-fold elevated in hirsute women. Thus, obesity is a state of increased androgen production and accelerated clearance. 3 alpha-diol G levels in obese women were only minimally elevated, in contrast to values in the hirsute women, perhaps reflecting the apparent androgen ineffectiveness.

Evidence of androgen action in endometrial and ovarian cancers

“…Furthermore, an analysis of EC cases in European women estimated that obesity accounted for 39% of cases (Bergstrom et al 2001), an association usually attributed to excess exposure to oestrogens as adipose tissue is the primary site of oestrogen production in post-menopausal women (Simpson et al 1997). Interestingly, a study from the 1980s by Samojlik et al (1984) examined androgen production in morbidly obese, non-hirsute, normally menstruating women and found that testosterone and dihydrotestosterone (DHT) production rates were elevated twofold compared with controls, but that this increased androgen production was offset by enhanced metabolic clearance. Despite the enhanced clearance described by the authors, the enhanced serum concentrations of androgens suggest that obesity may be a hyperandrogenic state.…”

Body composition, not body weight, is related to cardiovascular disease risk factors and sex hormone levels in men.

“…A fasting venous blood sample was obtained in the morning after an overnight (12 h) fast from an antecubital vein. Plasma estradiol and testosterone were measured by radioimmunoassay after diethyl ether extraction and Celite chromatography, with minor modifications of previously reported procedures (23,24). Sex-hormone binding globulin (SHBG) was determined by ammonium sulfate precipitation according to the method of Rosner (25).…”

THERAPY OF ENDOCRINE DISEASE: Treatment of hirsutism in the polycystic ovary syndrome

“…A significant decrease in production rate and blood levels of sex hormone-binding globulin (SHBG) is inversely correlated with body weight and particularly with the expansion of visceral fat, due to the inhibitory action of higher insulin concentrations (36). The decrease in the concentration of SHBG in blood results in an increase in circulating SBG-bound steroids, specifically testosterone (37), although an increase in their production rate may occur, particularly in those with the abdominal obesity phenotype (38). Interestingly, blood concentrations of androgens are paralleled to those observed in the fat tissue, specifically the visceral fat (39).…”