RESUMO
Women with polycystic ovary syndrome (PCO) display disordered patterns of LH pulsatility and may have an impairment of opioidergic regulation of GnRH-LH. In order to ascertain if these patterns reflect an inherent hypothalamic abnormality or a functional state consequent to the acyclicity of sex steroids, LH pulsatility and gonadotrophin responses to naloxone were examined in six PCO women before and after treatment with incremental daily doses of a progestogen, medroxyprogesterone acetate (MPA), for 10 days to determine (i) if progestogen treatment would alter the LH pulse pattern to resemble that of the luteal phase; and (ii) if the conversion to a luteal phase LH pulse pattern by MPA would involve the induction of opioidergic regulation. LH pulsatility and FSH levels were determined by blood sampling at 10 min intervals for 8 h before and after MPA treatment during a saline infusion on the control day and during a naloxone infusion (1.6 mg/h) on the following day. Basal levels of oestradiol, oestrone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate were measured before and after MPA. All six PCO women responded to MPA administration with a significant reduction in LH pulse frequency (P less than 0.005), an increase in LH pulse amplitude (P less than 0.0025), and an increase in LH pulse duration (P less than 0.025), without changes in mean LH, mean FSH, androgen, or oestrogen levels. Thus, a luteal phase LH pulse pattern was induced by MPA. Naloxone reversed the MPA-induced changes in LH pulsatility, indicating that these responses involved the induction of central opioidergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
PIP: To determine whether the disordered patterns of luteinizing hormone (LH) pulsatility and impaired opioidergic regulation of gonadotropin- releasing hormone (GnRH)-LH observed in women with polycystic ovarian syndrome reflect an inherent hypothalamic abnormality or a functional state related to the acyclycity of sex steroids, medroxyprogesterone acetate was administered to 6 women with this syndrome. It was hypothesized that if the apparent lack in women with polycystic ovarian syndrome of opiodergic regulation of GnRH-LH release was in fact secondary to an inherent hypothalamic defect, then the administration of this progestogen would fail to produce opiodergic regulation of GnRH-LH. Medroxyprogesterone acetate was given orally to the 6 study subjects over a 10-day period in an incremental dosage to mimic the luteal phase. LH pulsatility and follicle-stimulating hormone (FSH) levels were measured at 10 minute intervals during the 8 hours before and after treatment and infusions of saline or naloxone were given. All 6 subjects showed significant changes in LH pulsatile activities after steroid administration, specifically a slowing of LH pulse frequency and an increase in pulse amplitude and duration. Naloxone infusion reversed these progestogen-associated changes. There were no changes in mean LH, mean FSH, androgen, or estrogen levels, however, suggesting that a luteal phase LH pulse pattern was produced. Since naloxone reversed the changes in LH pulsatility induced by medroxyprogesterone acetate, it can be concluded that these responses involved the induction of central opiodergic activity secondary to ovarian acyclycity and progesterone deficiency, not a primary hypothalamic defect.
