Role of progesterone deficiency in the development of luteinizing hormone and androgen abnormalities in polycystic ovary syndrome.

The aetiology of polycystic ovary syndrome (PCOS) is unknown. It is uniquely characterized by oligomenorrhoea or amenorrhoea associated with normal or high oestrogen levels. This prospective clinical study was designed to examine the possible role of the lack of cyclical exposure to progesterone in the development of gonadotrophin and androgen abnormalities in PCOS. Gonadotrophin, androgen and oestrogen levels were measured in 15 PCOS patients and 10 normal subjects untreated and following treatment with the progestogen medroxyprogesterone acetate (MPA). When compared to control subjects, PCOS patients had significantly higher luteinizing hormone (LH) pulse height, pulse amplitude, integrated LH levels, LH response to gonadotrophin-releasing hormone (GnRH) and LH/FSH ratio; LH pulse frequency was similar in the two groups. In addition, the testosterone/sex hormone binding globulin ratio (T/SHBG), androstenedione and oestrone concentrations in the plasma were significantly higher in PCOS than in control subjects. When PCOS patients were treated with MPA for 5 days, there were significant decreases (p < 0.02-0.001) to values no longer different from normal: from 8.7 +/- 1.2 to 5.6 +/- 0.8 IU/l for integrated LH levels (untreated and MPA-treated PCOS); from 31.2 +/- 3.5 to 12.9 +/- 1.5 IU/l for LH response to GnRH; from 2.4 +/- 0.26 to 1.3 +/- 0.2 for LH/FSH ratio; and from 10.4 +/- 0.63 to 8.5 +/- 0.7 nmol/l for androstenedione. Significant decreases (p < 0.05-0.005) to values that still remained significantly higher than in normal subjects occurred for: LH pulse height, 11.05 +/- 1.3 to 6.88 +/- 0.79 IU/l (untreated and MPA-treated PCOS); LH pulse amplitude, 2.8 +/- 0.5 to 1.8 +/- 0.2 IU/l; total testosterone, 2.5 +/- 0.2 to 2.0 +/- 0.2 nmol/l; T/SHBG ratio, 14.1 +/- 1.7 to 11 +/- 1.5; and oestrone, 265 +/- 24 to 208 +/- 29 pmol/l. These results are consistent with the concept that ovulation failure and progesterone deficiency play a facilitatory role in the development of the hypothalamic-pituitary abnormality giving rise to disordered LH secretion in PCOS.