The use of a combined regimen of GnRH agonist plus a low-dose oral contraceptive improves the spontaneous pulsatile LH secretory characteristics in patients with polycycstic ovary disease after discontinuation of treatment.

PURPOSE: The fertility rate in women with polycystic ovary disease (PCOD) is influenced by the type of treatment received. The present study evaluated the possible correlation between treatment and pulsatile release of gonadotropins. METHODS: Spontaneous episodic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and hormonal parameters were monitored before and after 1, 3, and 6 months after treatments suspension. Twenty-four PCOD patients were randomly divided into two groups of 12 subjects. Group A was treated with gonadotropin-releasing hormone (GnRH)-analogue plus oral contraceptive (OC). Group B was treated only with OC. Both groups were treated for 6 months and followed up for 6 months. RESULTS: In all subjects the therapeutic regimens reduced the androgenic milieau and the gonadotropin plasma levels. Spontaneous pulsatile secretion of LH and FSH was significantly modified in both groups, but patients who received the combined regimen showed a significantly greater reduction of LH plasma levels and a significantly greater decrease of LH pulse amplitude throughout the 6 months after treatment suspension. Ferriman-Gallway score and ovarian volumes were significantly reduced in patients who received the combined treatment than in the OC-treated patients. CONCLUSIONS: These data support the evidence of a higher efficacy of the combination of GnRH-a + OC than OC alone in restoring a normal and adequate spontaneous episodic gonadotropin discharge and in decreasing Ferriman-Gallway score and ovarian volumes in patients with PCOD.

Estrogen replacement therapy modulates spontaneous GH secretion but does not affect GH-RH-induced GH response and low T3 syndrome in women with hypothalamic amenorrhea associated to weight-loss.

Severe dieting and negative energy balance usually lead to the occurrence of amenorrhea together with several endocrine disturbances such as the "low T3 syndrome" and an abnormal GH secretion. To evaluate whether estrogen replacement therapy (ERT) affects thyroid hormones and GH secretion, two groups of patients affected by weight-loss-related amenorrhea and with low plasma T3 levels were treated with two different schedules of ERT using 50 or 100 micrograms estradiol transdermal patches twice a week (Dermestril, Rottapharm, Monza, Italy). Before and after 5 weeks of therapy in each patient thyroid hormones, spontaneous GH secretion and GH-RH-induced GH release were evaluated. After ERT, plasma GH and IGF-1 levels increased in both groups and a consistent change in GH spontaneous release was observed. Conversely the low T3 plasma levels and GH-RH-induced GH response were not modified by ERT. Our present data suggest that in amenorrhea related to weight-loss, hormonal abnormalities are only in part dependent from the hypoestrogenic condition.

Modulatory effects of a synthetic steroid (tibolone) and estradiol on spontaneous and GH-RH-induced GH secretion in postmenopausal women.

OBJECTIVE: Since hormonal replacement therapy (HRT) affects plasma GH levels, the present study aimed to verify the effect of tibolone, a synthetic steroid, on modulating spontaneous and growth hormone releasing hormone (GH-RH) induced GH secretion. METHODS: Postmenopausal women (n = 30) were enrolled and randomly subdivided in three groups (n = 10 each group): (1) treated with transdermal estradiol (50 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (2) treated with transdermal estradiol (100 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (3) treated with tibolone 2.5 mg/day (Livial, Organon Italia, Rome, Italy). Patients underwent a GH-RH test (1 microgram/kg) and 15 of them underwent to a pulsatility study before and 5 weeks after treatment. RESULTS: Mean (+ S.E.M.) GH plasma levels increased in all patients after any type of HRT. GH response to GH-RH stimulation (expressed as maximal response to GH-RH or as delta value) was similar in the three groups while significant changes occurred in spontaneous pulsatile GH release. Tibolone and both dosages of transdermal estradiol significantly reduced GH pulse frequency and increased pulse amplitude. CONCLUSIONS: The reduced plasma GH levels observed during postmenopause are probably related to a reduced endogenous GH-RH and not to a reduced pituitary ability to respond to GH-RH. In addition tibolone, as well as transdermal estradiol, are effective in restoring the spontaneous GH episodic release.

A long-term treatment with gonadotropin-releasing hormone agonist plus a low-dose oral contraceptive improves the recovery of the ovulatory function in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the hormonal and clinical follow-up after the suspension of a longterm therapy with GnRH-agonist (GnRH-a) plus oral contraceptive (OC) in comparison to OC alone in patients with polycystic ovary syndrome (PCOS). DESIGN: Hormonal (plasma LH, FSH, sex steroid levels) and clinical (Ferriman-Gallwey score and ultrasound) parameters were monitored at various moments during the 6 months of treatment and during the 6 months after treatment suspension. SETTING: Physiopathology of Human Reproduction, University of Modena, Italy. PATIENT(S): Thirty patients with PCOS were enrolled and randomly subdivided in two groups of 15 each. INTERVENTION(S): Group A was treated with 3.75 mg IM GnRH-a plus OC. Group B was treated only with OC. RESULT(S): Both therapeutical regimens were effective in reducing androgenic milieu, Ferriman-Gallwey score, and ovarian volume within the 6th month of treatment. However, only patients treated with GnRH-a + OC showed a normal LH:FSH ratio, adequate plasma E2 and P levels, and ovulatory cycles during the 6 months of the after treatment follow-up. Patients treated with OC alone showed no beneficial effect after the 3rd month of the follow-up. CONCLUSION(S): These data support the evidence of a higher efficacy of the combined regimen (GnRH-a + OC) than OC alone in the treatment of patients with PCOS. In addition, the former regimen is associated with recovery of normal ovulatory cycles.

Growth hormone (GH)-releasing hormone-induced GH response in hypothalamic amenorrhea: evidence of altered central neuromodulation.

OBJECTIVE: To evaluate the GH-releasing hormone (GH-RH)-induced response of GH in patients affected by hypothalamic amenorrhea. DESIGN: Patients affected by weight-loss-related hypothalamic amenorrhea (n = 28) were studied and compared with 20 healthy controls. Among patients with weight-loss amenorrhea, both hypogonadotropic and normogonadotropic conditions were present. All subjects underwent a GH-RH test (GEREF, Sereno, Rome, Italy) (1 microgram/kg body weight IV). Plasma GH concentrations were determined using commercially available RIAs. Also, in selected samples insulin-like growth factor-I (IGF-I) levels were measured. RESULTS: Basal plasma IGF-I levels as well as body mass index (BMI) were lower in amenorrheic patients than in healthy controls. No significant correlation was found between BMI and IGF-I or E2 plasma levels or between LH and IGF-I plasma levels. The basal GH plasma levels were comparable in all groups of subjects. The GH-RH--induced GH response evaluated as maximal release and as area under the curve (AUC) was higher in amenorrheic patients than in control subjects. CONCLUSIONS: The amenorrheic condition associated with reduced BMI changes the GH-RH--induced GH response in hypothalamic amenorrhea, supporting a GH and a IGF-I disregulation in weight-loss--related amenorrhea.

Naltrexone treatment restores menstrual cycles in patients with weight loss-related amenorrhea.

OBJECTIVE: To evaluate whether the efficacy of naltrexone administration in patients with hypothalamic amenorrhea correlates to the response to an acute naloxone test. DESIGN: Thirty patients with hypothalamic amenorrhea associated with weight loss were studied. After naloxone test (4 mg in bolus IV) patients were divided into two groups: group A, nonresponsive (n = 15) and group B, responsive (n = 15). Group A underwent two cycles of hormonal replacement therapy with E2 patches and medroxyprogesterone acetate. Then all patients were administered naltrexone at the dosage 50 mg/d orally for 6 months. A third group of 10 amenorrheic patients were treated with oral placebo with the same schedule. RESULTS: Plasma gonadal steroid levels increased in all patients and in 24 of 30 patients the menstrual bleeding occurred within 90 days from the beginning of treatment. After 6 months from naltrexone discontinuation, 18 of 24 patients still showed the occurrence of menstrual cycles. Luteinizing hormone plasma levels and LH pulse amplitude increased after 3 months of treatment and remained unchanged 6 months after naltrexone suspension. Plasma FSH levels did not show any change in any patient. The body mass index increased after 3 months in all patients who menstruated. Patients treated with placebo did not show any significant change in gonadotropins and gonadal steroid plasma levels. CONCLUSIONS: The present study supports the efficacy of naltrexone therapy for patients with hypothalamic amenorrhea either responsive or nonresponsive to naloxone test.