Spontaneous reversibility of bone loss induced by gonadotropin-releasing hormone analog treatment.

OBJECTIVE: To verify if a 6-month period of hypoestrogenism due to chronic treatment with GnRH analogue (GnRH-a) causes irreversible bone loss in young women. DESIGN: Controlled clinical study in volunteer women. SETTING: Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. PATIENTS: Twenty-eight women (mean age +/- SE 81.1 +/- 0.99 years) with endometriosis diagnosed by laparoscopy and 25 healthy, normally cycling women of the same age (28.3 +/- 1.14 years). INTERVENTIONS: In women with endometriosis, six SC implants of the GnRH-a compound, 3.6 mg goserelin acetate depot, were administered every 28 days starting within 15 days of laparoscopy. Compounds interfering with bone metabolism or hormonal formulations were not taken by control women during the entire period of the study. MAIN OUTCOME MEASURE: Evaluation of lumbar bone mineral density at the start of the study and 6, 12, and 30 months later. RESULTS: At the onset of the study, lumbar bone mineral density did not differ in women with endometriosis and control women. Lumbar bone mineral density values significantly decreased after 6 months of GnRH-a treatment. This reduction was still evident 6 months after GnRH-a interruption. However, 24 months after treatment withdrawal, bone mineral density reduction disappeared and bone mineral density values were completely superimposable (+/- O.4 percent) to those observed before treatment. In contrast, control women lumbar bone mineral density values did not change during the entire period of observation. CONCLUSIONS: These data suggest that GnRH-a treatment for 6 months is not associated with long-term effects on lumbar bone density.

Involvement of ovarian factors magnified by pharmacological induction of multiple follicular development (MFD) in the increase in Ca125 occurring during the luteal phase and the first 12 weeks of induced pregnancies.

OBJECTIVE: To evaluate the relationship of ovarian activity on Ca125 production, we studied whether Ca125 production varies during the menstrual cycle both in normal ovulatory women and in women whose ovarian factors are significantly stimulated by multiple follicular development (MFD). Furthermore, since the first 12 weeks of pregnancy is characterized by the enhancement of corpus luteum function mainly in MFD-induced pregnancies, Ca125 levels were also evaluated in the first quarter of pregnancy both in spontaneous and in MFD-induced pregnancies. SUBJECTS: Subjects were normal ovulatory women in the late follicular phase (FP) (N = 20) and in the luteal phase (LP) (N = 20), 32 infertile women submitted to MFD with pure FSH, and 40 pregnant women in which pregnancy occurred spontaneously (N = 20) or after induction of MFD (N = 20). RESULTS AND CONCLUSIONS: In regularly cycling women plasma Ca125 levels were constant during the menstrual cycle. In contrast, in stimulated cycles Ca125 levels were significantly higher (P < 0.0008) in the LP than in the FP. In addition, in these subjects Ca125 levels in the LP were significantly correlated (P < 0.0001, r = 0.686) with E2 plasma levels. These data strongly suggest that an increase in corpus luteum function could be involved in Ca125 production. Since granulosa cells have not been demonstrated to produce Ca125, it can be hypothesized that endometrial or peritoneal cells submitted to exaggerated stimulation by ovarian activity are the source of increased Ca125 secretion. In agreement with this hypothesis, Ca125 levels were significantly higher in the first weeks of spontaneous pregnancies than in the luteal phase and they were also higher in MFD-induced pregnancies than in spontaneous pregnancies (P < 0.001).

Shrinkage of pituitary PRL-secernent adenoma after short-term treatment with bromocriptine long-acting repeatable injections.

The efficacy, safety and tolerability of a single bromocriptine-LAR injection (50 mg) and of a 6 injection course at 28-day intervals, were evaluated respectively in 13 and in 9 hyperprolactinemic women with radiological signs of PRL-secreting pituitary adenoma. The long-lasting repeatable formulation of bromocriptine induced a rapid and prolonged hypoprolactinemic effect. Side effects related to central activity of the compound were observed only on the first day of compound administration in all subjects except one, whereas no modifications of cardiologic and haematologic parameters were observed. In one subject the occurrence of side effects was observed also during the 6 injection course of treatment. A significant shrinkage of pituitary adenoma was observed at the second CT scan performed in 7 of the 9 subjects treated for 6 months with bromocriptine-LAR. CT scan was not performed in one subject who achieved pregnancy after second bromocriptine-LAR injection, whereas unmodified size of pituitary microadenoma was found in one subject whose PRL secretion did not decrease during the treatment and who referred severe side effects.