The role of insulin in ovarian size in patients with the polycystic ovary syndrome.

The objective of this study was to evaluate whether the degree of suppression of ovarian volume effected by a gonadotropin releasing hormone (GnRH) agonist in patients with polycystic ovary syndrome (PCOS) correlated with basal insulin secretion and insulin secretion provoked by a glucose challenge. Eighteen PCOS patients received the GnRH agonist D-tryptophan-6-LHRH (Decapeptyl, 3.75 mg monthly i.m.) for 6 months and had blood glucose and insulin measured during a 75 g oral glucose tolerance test (OGTT) prior to and at the end of therapy. According to ovarian volume suppression after GnRH agonist therapy, two groups were defined: in group A (n = 10; mean body mass index (BMI) +/- SEM, 25.6 +/- 1.6 kg/m2) ovarian volume regressed from 17.9 +/- 1.6 to 6.7 +/- 0.3 ml (full responders) and in group B (n = 8; mean BMI +/- SEM, 28.1 +/- 2.3 kg/m2) from 21.5 +/- 1.1 to 15.1 +/- 1.0 ml (partial responders). Results showed that GnRH agonist therapy did not affect significantly BMI or fasting levels and area under the curve (AUC) for glucose and insulin in the respective groups. Fasting insulin levels correlated positively with ovarian volume prior to (r = 0.56, p < 0.05) and after 6 months of GnRH agonist therapy (r = 0.80, p < 0.005). The suppressibility of ovarian volume with GnRH agonist therapy correlated negatively with the difference between maximal and basal levels (r = -0.68), the area under the curve (r = -0.62) and maximal levels (r = -0.72) for insulin during the OGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Octreotide effect on ovarian morphology in insulin-resistant PCOS patients following six-month decapeptyl treatment.

PROBLEM: Regulation of ovarian folliculogenesis involves bidirectional communication between the immune and endocrine systems. Somatostatin analogues have been reported to acutely suppress elevated androgens in polycystic ovary syndrome (PCOS). The aim of our study was to analyze the morphologic and hormonal-metabolic response to octreotide therapy for one month in insulin-resistant PCOS patients in whom luteinizing hormone (LH) effect had formerly been separated by a six-month GnRH-agonist (GnRH-a) course. METHOD: Fifteen PCOS patients were studied two months after completing a six-month GnRH-a (decapeptyl 3.75 mg monthly injection) course. Seven of the patients (group A), who were insulin-resistant and gave hyperinsulinemic response to a glucose challenge, received a 50-micrograms subcutaneous injection of octreotide twice a day for one month. The nonhyperinsulinemic patients (group B) received placebo injections. Hormonal measurements, oral glucose tolerance test (OGTT), and transvaginal ovarian ultrasound were performed before and toward the end of the treatment period. RESULTS: After octreotide ovarian volume dropped significantly in group A (x +/- SD) (19.2 +/- 5.1 versus 14.7 +/- 5.5 cc, P = .02). LH levels increased (3.25 +/- 1.22 versus 5.95 +/- 4.34 mu/ml, P = .05) as did E2 levels (38.0 +/- 11.4 versus 55.1 +/- 12.7 pg/ml, P = .005). There was no change in follicle-stimulating hormone, 17-hydroxy-progesterone, free testosterone, or androstenedione levels. Insulin secretion during OGTT dropped significantly (555 +/- 294 versus 68 +/- 29 mu u/ml/hr, P = .002). Glucose tolerance was not affected. In contrast, the placebo-treated group B patients showed an increase in ovarian volume (10.9 +/- 3.5 versus 14.8 +/- 3.3 cc, P = .001) while their gonadotropin and steroid profile relapsed, similarly to our patients receiving octreotide. CONCLUSIONS: Octreotide has an adjunctive beneficial effect to GnRH-a on ovarian morphology although, at the dose used, there was no suppression of gonadotropin or ovarian steroid levels. The changes in ovarian morphology are probably mediated through suppression of insulin levels and/or other ovarian growth factors.

Hypercalcemia of cancer: an update.

Hypercalcemia of cancer is due to secretion of substances with parathyroid hormone (PTH)-like activity from tumours of the respiratory, gastrointestinal and urogenital tract as well as hematologic malignancies and breast cancer. PTH-related Protein (PTHrP) is secreted mainly from solid tumours and it has been recently recognized as being responsible for hypercalcemia mediated primarily via an increased renal reabsorption of calcium and secondly by an increased bone resorption. PTHrP-mRNA is expressed in a variety of normal tissues and has multiple physiologic and paracrine actions. Bone resorbing factors like the cytokines-lymphokines, interleukins, prostaglandins, TNF-alpha/TNF-beta, GM-CSF/G-CSF, TGF-alpha and TGF-beta are produced by certain solid and hematologic cancers and have also been implicated in tumour-induced hypercalcemia. The recently introduced PTHrP antagonists are hopeful therapeutic measures for the future.

Therapeutic use of gonadotropin-releasing hormone agonists in polycystic ovarian syndrome.

Polycystic ovarian syndrome is a heterogeneous disorder characterized by abnormal function of the hypothalamic-pituitary-gonadal axis, excessive production of androgens, aberrant intermediary metabolism, and structural changes in ovarian morphology. Long-term administration of the GnRH agonistic analogues brings about pituitary gonadotroph down-regulation after an initial period of stimulation of FSH/LH release. The resulting decrease in LH output and ovarian androgen production exerts beneficial effects on the clinical and biochemical parameters of the PCO syndrome. Ovarian volume and stroma usually decrease, but the results of treatment are not permanent, since relapse of the syndrome is usually observed a few months after cessation of the agonist. There are no serious side effects, and a small decrease in bone mineral content is recovered after discontinuation of the treatment. Possible indications for this regime include patients with very large ovaries and resistant hyperandrogenemia. On the other hand, the use of GnRH agonists in the preparation of PCOS patients for ovulation induction is already established.