[The role of the endogenous opioid system in the pathogenesis of polycystic ovary syndrome: the altered neuroendocrine regulation of GnRH-LH is corrected after clomiphene therapy].
To investigate whether inappropriate LH secretion in Polycystic Ovary Syndrome (PCO) was related to a reduction of inhibitory opioid control on the GnRH-LH system, 23 women affected by PCO (12 obese, BMI: 37.1 +/- 3.9 and 11 non obese, BMI: 21.5 + 2.4) and 19 fertile women (10 obese, BMI: 38.8 + 1.8 and 9 non obese, BMI: 20.1 + 1.5) were studied. Plasma levels of Beta-Endorphin (B-Ep) in basal condition and LH and FSH serum levels following acute administration of naloxone (0.1 mg/kg e.v.) were evaluated in the PCO and control groups. Moreover, in order to investigate whether the neuroendocrine abnormalities in PCO are a primary hypothalamic defect or secondary to an inappropriate feedback of gonadal steroids, the LH response following Naloxone administration was evaluated again after two months of clomiphene therapy (50 mg p.os ones a day for 5 days). The women affected by PCO had increased LH/FSH ratio, testosterone levels (P < 0.001, P < 0.01) and significantly decreased T/E2 ratio, SHBG levels compared to the normal women (P < 0.01, P < 0.001). B-Ep plasma levels in PCOs OB and PCOs nOB (6.13 + 1.2 Pmol/L, 4.8 + 0.4 Pmol/L) were similar to those observed in obese and non obese control women (7.2 + 2.5 Pmol/L, 4.2 + 1.3 Pmol/L), respectively. In the PCO and control groups naloxone induced a significant increase of FSH and LH levels. Thus the area under the curve of LH and FSH was significant higher after naloxone, than following saline infusion both in PCO (P < 0.01, P < 0.05) and controls (P < 0.001, P < 0.001). However, in PCO the post naloxone FSH increase was similar to that found in fertile women, while the LH increase post naloxone was lower than that observed in controls (50 + 32.4% vs 101.6 + 36.7%; P < 0.01). Particularly in PCO with LH/FSH ratio equal or higher than 3, no significant variation of LH levels was found after naloxone. Moreover the LH increase post naloxone was similar in PCO OB (46 + 19.8%) and in PCO nOB (49.9 + 13.1%), correlated negatively with LH basal levels (P < 0.02), LH/FSH (P < 0.005), E1/E2 (P < 0.005) and was independent of T/E2, BMI and duration of the disease. Following clomiphene treatment, the LH response after naloxone was significantly higher than that observed before treatment (from 9.4 + 4.2 mUI/ml to 16.5 + 3.9 mUI/ml, P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
Barletta
C
C
Policlinico Umberto I, Roma.
Vagiri
D
D
Scavo
D
D
D000293:Adolescent; D000328:Adult; D002996:Clomiphene / Q000627:therapeutic use*; D004723:Endorphins / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000503:physiopathology*
D004723:Endorphins; D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone
Il ruolo del sistema oppioide endogeno nella patogenesi della sindrome dell'ovaio policistico: l'alterata regolazione neuroendocrina di GnRH-LH si corregge dopo terapia con clomifene.