A Direct Effect of Hyperinsulinemia on Serum Sex Hormone-Binding Globulin Levels in Obese Women with the Polycystic Ovary Syndrome*

Abstract

To determine whether hyperinsulinemia can directly reduce serum sex hormone-binding globulin (SHBG) levels in obese women with the polycystic ovary syndrome, six obese women with this disorder were studied. Before study, ovarian steroid production was suppressed in each woman by the administration of 7.5 mg of a long-acting GnRH agonist, leuprolide depot, im, on days -56, -28, and 0. This resulted in substantial reductions in serum concentrations of testosterone (from 1.72 +/- 0.29 nmol/L on day -56 to 0.32 +/- 0.09 nmol/L on day 0), non-SHBG-bound testosterone (from 104 +/- 16 pmol/L on day -56 to 19 +/- 5 pmol/L on day 0), androstenedione (from 7.25 +/- 1.65 nmol/L on day -56 to 2.78 +/- 0.94 nmol/L on day 0), estrone (from 371 +/- 71 pmol/L on day -56 to 156 +/- 29 pmol/L on day 0), estradiol (from 235 +/- 26 pmol/L on day -56 to 90 +/- 24 pmol/L on day 0), and progesterone (from 0.28 +/- 0.12 nmol/L on day -56 to 0.08 +/- 0.02 nmol/L on day 0). Serum SHBG levels, however, did not change (18.8 +/- 2.8 nmol/L on day -56 vs. 17.8 +/- 2.6 nmol/L on day 0). While continuing leuprolide treatment, the women were administered oral diazoxide (300 mg/day) for 10 days to suppress serum insulin levels. Diazoxide treatment resulted in suppressed insulin release during a 100-g oral glucose tolerance test (insulin area under the curve, 262 +/- 55 nmol/min.L on day 0 vs. 102 +/- 33 nmol/min.L on day 10; P less than 0.05) and deterioration of glucose tolerance. Serum testosterone, androstenedione, estrone, estradiol, and progesterone levels did not change during combined diazoxide and leuprolide treatment. In contrast, serum SHBG levels rose by 32% from 17.8 +/- 2.6 nmol/L on day 0 to 23.5 +/- 2.0 nmol/L on day 10 (P less than 0.003). Due primarily to the rise in serum SHBG levels, serum non-SHBG-bound testosterone levels fell by 43% from 19 +/- 5 pmol/L on day 0 to 11 +/- 4 pmol/L on day 10 (P = 0.05). These observations suggest that hyperinsulinemia directly reduces serum SHBG levels in obese women with the polycystic ovary syndrome independently of any effect on serum sex steroids.

Diabetes mellitus and risk of endometrial cancer: a meta-analysis

“…Long-term insulin therapy of patients with type 1 diabetes may explain the increased risk of endometrial cancer among diabetic women with type 1 diabetes [35]. Hyperinsulinaemia may also increase levels of bioactive oestrogens by decreasing concentrations of circulating sex hormone binding globulin [49,50]. Oestrogens have been shown to increase endometrial cancer risk by stimulating proliferation of endometrial cells [51], when unopposed by progesterone [52,53].…”

Lifetime recreational exercise activity and risk of breast carcinoma in situ

“…Higher levels of insulin and decreased insulin sensitivity have been associated with decreased levels of sex hormone-binding globulin and, consequently, a higher level of freeestradiol, which may increase the risk of breast carcinoma. 42 Family history of breast carcinoma modified the association between exercise activity and BCIS risk. No reduction in risk was observed among women reporting a first-degree family history of breast carcinoma.…”

Glycemic index in chronic disease: a review

“…The influence of estrogens on the breast is related to estrogen receptors which may be activated, among others, by insulin-like growth factors (Yee & Lee, 2000). Sustained high insulin levels may increase the risk of breast cancer by at least two possible routes: (1) suppression of sex hormonebinding globulin (SHBG) thereby rendering free circulating estradiol more available for action at the tissue level; (2) suppression of IGFBP-I, thus increasing free IGF-1 levels (Plymate et al, 1990;Nestler et al, 1991).…”