Session: MON 548-560-Hyperandrogenic Disorders
Poster Board MON-559
We assessed the effect of metformin on P suppression of LH (GnRH) pulse frequency in HA girls (n = 6, Tanner stage 5, mean age 15.2 ± 0.3 SEM). Girls had q 10 min LH sampling overnight and 75-g oral glucose tolerance testing (OGTT) the next morning. They received 7 days of oral E2/P, then repeated overnight LH sampling. Girls took metformin (1000 mg BID) for 10 weeks and then repeated the OGTT and LH sampling before and after E2/P. Results are presented as mean ± SEM. The percent change of LH pulse number divided by day 7 P level was used to assess hypothalamic P sensitivity (10.3 ± 7.7 in NW Tanner 3-5 girls ).
At baseline, 5 of 6 HA girls were P-insensitive similar to adult PCOS (2). P sensitivity increased overall (3.54 ± 0.95 pre- vs. 5.53 ± 1.34 post-) and improved in 5/6 after metformin (2 girls moved to normal range) (1). Although fasting insulin levels did not improve (27.0 ± 6.6 vs. 27.5 ± 8.2 mIU/ml), metformin reduced AUC insulin during OGTT by 25% (12903 ± 2546 vs. 9631 ± 3490 mIU/mL). Morning free testosterone (T) decreased 20% (46.2 ± 10.0 vs. 37.4 ± 10.3 pmol/L) after metformin. Sex hormone binding globulin was unchanged after metformin (18.7 ± 6.4 vs 20.3 ± 8.1 nmol/L), suggesting decreased free T was due to less total T production.
These results suggest that metformin modestly improves hypothalamic P sensitivity. Fasting insulin did not change, but stimulated insulin and morning free T improved by 20-25% in HA girls. Over a longer period of treatment, we speculate that metformin may provide an even greater benefit for P sensitivity in HA girls. Further studies are needed to delineate mechanisms by which metformin improves hypothalamic P sensitivity.
Nothing to Disclose: CMB, JSPC, JPB, ADA, RB, CRM, JCM
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