Women with the polycystic ovary syndrome (PCO) have significant insulin resistance and are at risk to develop noninsulin-dependent diabetes mellitus. It remains controversial, however, whether hyperandrogenism directly decreases insulin action. Hence, we performed 2-h euglycemic glucose (approximately 772 pmol/L steady state insulin levels) clamps in nine PCO women with insulin resistance basally and after the 12th week of therapy with a superagonist GnRH analog (40 micrograms every 8 h, sc). Diet, activity, and weight were kept constant. Despite significant decreases in plasma testosterone and androstenedione levels (both P less than 0.05), there was no significant change in insulin-mediated glucose disposal, plasma insulin levels, or hepatic glucose production. The sample size was adequate to detect a clinically significant change in insulin-stimulated glucose disposal (i.e. approximately 3.3 mumol/kg.min; P less than or equal to 0.05). We conclude that suppressing androgen levels into the normal range did not result in significant changes in insulin resistance in PCO. Thus, controlling hyperandrogenemia is not a clinically effective modality to improve insulin action and thereby decrease the risk of noninsulin-dependent diabetes in PCO.

Suppression of Hyperandrogenism Does not Improve Peripheral or Hepatic Insulin Resistance in the Polycystic Ovary Syndrome

Forty years of IVF

Progesterone levels on the day of human chorionic gonadotropin administration in cycles with gonadotropin-releasing hormone agonist suppression are not predictive of pregnancy outcome

Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

Routine pituitary suppression with leuprolide before ovarian stimulation for oocyte retrieval

In eumenorrheic women with endometriosis and in oligo-amenorrheic women with polycystic ovarian disease (PCO), chronic administration of a long-acting GnRH agonist (GnRH-a) reduced the circulating concentrations of estrogens and androgens to levels similar to those of castrated women. The concommittant elevation of LH in both groups suggested that the measured immunoreactive LH had reducedbioactivity. In seven women with endometriosis, bioactive LH (BA LH) measured as the in-vitro secretion of testosterone by dispersed Leydig cells, was significantly (p < 0.001)reduced from 10.8 ± 1.2 (SEM) to 4.4 ± 0.2 mlU/ml at the end of 28 days of GnRH-a therapy. In five women with PCO, BA LH decreased from 44.2 ± 15.5 to 5.7 ± 0.6 mlU/ml(p = 0.06). These changes of BA LH appeared to be responsible for the suppression of ovarian androgen secretion during GnRH-a treatment and in turn may have contributed to the profound decreases of estrogen production by reducing the amount of precursor androgen available for aromatiz...

Z. Tsao

Papers

Stimulation of LH fragments with reduced bioactivity following GnRH agonist administration in women.