A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome.
Level 4 - case-series / case-control
Uncontrolled before-after interventional study in a small clinical series
PubMed 1898744 · doi:10.1210/jcem-72-1-83
What was done
Six obese women with polycystic ovary syndrome (PCOS) underwent ovarian steroid suppression with the GnRH agonist leuprolide depot (7.5 mg im on days -56, -28, and 0). While maintaining leuprolide, participants received oral diazoxide (300 mg/day) for 10 days to inhibit pancreatic insulin secretion. Serum sex steroids, sex hormone-binding globulin (SHBG), and insulin response to a 100-g oral glucose tolerance test (OGTT) were measured before and after diazoxide.
What was found
Leuprolide alone reduced total testosterone (1.72 ± 0.29 to 0.32 ± 0.09 nmol/L), non-SHBG-bound testosterone (104 ± 16 to 19 ± 5 pmol/L), androstenedione (7.25 ± 1.65 to 2.78 ± 0.94 nmol/L), estrone (371 ± 71 to 156 ± 29 pmol/L), estradiol (235 ± 26 to 90 ± 24 pmol/L), and progesterone (0.28 ± 0.12 to 0.08 ± 0.02 nmol/L), without altering SHBG (18.8 ± 2.8 to 17.8 ± 2.6 nmol/L). Subsequent diazoxide administration reduced OGTT insulin area under the curve from 262 ± 55 to 102 ± 33 nmol/min·L (P < 0.05). During diazoxide treatment, sex steroid levels remained suppressed and unchanged, but serum SHBG rose by 32% from 17.8 ± 2.6 to 23.5 ± 2.0 nmol/L (P < 0.003), and non-SHBG-bound testosterone dropped by 43% from 19 ± 5 to 11 ± 4 pmol/L (P = 0.05).
Why it matters
This study provides experimental evidence that hyperinsulinemia directly lowers circulating SHBG levels in obese women with PCOS independently of ovarian sex steroids.
Limits
The study is limited by an extremely small sample size (n = 6) and the absence of a parallel control group. Diazoxide was administered for only 10 days and caused deterioration of glucose tolerance, serving as an experimental probe rather than a practical therapeutic intervention.
Cited by
- supports A lack of insulin signaling reduces the physiological capacity to suppress sex hormone binding globulin (SHBG).