leuprolide and Hyperinsulinism

Topics: Body Height; Body Mass Index; Child; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Hyperandrogenism; Hyperinsulinism; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Leuprolide; Menarche; Menstrual Cycle; Pelvis; Ultrasonography

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol. Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization. Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/ naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.

Topics: Adult; Androgens; Estradiol; Female; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Kinetics; Leuprolide; Luteinizing Hormone; Naltrexone; Narcotic Antagonists; Opioid Peptides; Ovary; Polycystic Ovary Syndrome; Steroids

Ovarian hyperandrogenism from polycystic ovary syndrome (PCOS) and hyperinsulinemia from insulin resistance are modulators of ovarian follicle development. We report on a woman with PCOS and hyperandrogenism and severe insulin resistance from metabolic syndrome who received long-term GnRH analogue therapy preceding bilateral salpingo-oophorectomy for massive ovarian enlargement. Ovarian histological examination showed proliferating granulosa cells within antral follicles coexistent with serous cystadenofibromas, demonstrating a unique link between hyperinsulinemia and granulosa cell mitogenesis.. A 30-year-old woman with PCOS with hyperandrogenism, severe insulin resistance from metabolic syndrome, and nonalcoholic steatohepatitis experienced abdominal pain from bilaterally enlarged ovaries. She had previously experienced a pulmonary embolism while taking oral contraceptives and hepatotoxicity from metformin and spironolactone therapies. Long-term GnRH analogue therapy to induce pituitary desensitization to GnRH successfully decreased gonadotropin-dependent steroidogenesis without improving insulin resistance. Despite GnRH analogue therapy, progressive ovarian enlargement in the presence of hyperinsulinemia from worsening metabolic function eventually required bilateral salpingo-oophorectomy for removal of massively enlarged ovaries. Histological examination showed both ovaries contained proliferating granulosa cells within antral follicles coexistent with serous cystadenofibromas.. In women with PCOS and hyperinsulinemia from severe insulin resistance due to metabolic syndrome, granulosa cell proliferation within antral follicles can occur despite long-term GnRH analogue therapy, implicating hyperinsulinemia as a granulosa cell mitogen in the absence of gonadotropin-dependent ovarian function.

Topics: Abdominal Pain; Adult; Cell Proliferation; Cystadenofibroma; Female; Fertility Agents, Female; Granulosa Cells; Humans; Hyperandrogenism; Hyperinsulinism; Insulin Resistance; Leuprolide; Organ Size; Ovarian Follicle; Ovarian Neoplasms; Polycystic Ovary Syndrome; Salpingo-oophorectomy; Severity of Illness Index; Tomography, X-Ray Computed; Ultrasonography

Hyperinsulinemia can lead to pathologic ovarian growth and androgen production.. A 29-year-old woman developed an autoantibody to the insulin receptor (type B insulin resistance), causing extreme insulin resistance and hyperinsulinemia. Testosterone levels were elevated to the adult male range. Treatment with gonadotropin-releasing hormone (GnRH) analog led to normalization of testosterone, despite persistent extreme insulin resistance.. This case demonstrates that gonadotropins are necessary for insulin to cause pathologic ovarian androgen production. Suppression of gonadotropins with GnRH analogs may be a useful therapeutic option in patients with severe hyperandrogenism or ovarian enlargement because of hyperinsulinemia.

Topics: Adult; Antineoplastic Agents, Hormonal; Autoantibodies; Cyclophosphamide; Dexamethasone; Diagnosis, Differential; Female; Gonadotropin-Releasing Hormone; Humans; Hyperandrogenism; Hyperinsulinism; Immunosuppressive Agents; Insulin Resistance; Leuprolide; Ovarian Diseases; Receptor, Insulin; Rituximab; Testosterone

To evaluate the ovarian function during early infancy in daughters of women with polycystic ovary syndrome (PCOS) treated with metformin throughout pregnancy (PCOSd+M), as a means to reduce androgen and insulin levels, compared with daughters of nontreated PCOS women (PCOSd-M) and daughters of women who belong to a healthy comparison group (HCd).. Descriptive and analytic study.. Unit of endocrinology and reproductive medicine.. Fifteen PCOSd+M, 23 PCOSd-M, and 35 HCd were studied at 2-3 months of age.. A GnRH analogue test was performed with determinations of gonadotropins, sex steroids, SHBG, and anti-Müllerian hormone (AMH).. Differences in AMH levels between PCOSd+M, PCOSd-M and HCd.. AMH and peak E(2) concentrations were significantly higher in PCOSd-M compared with HCd, whereas PCOSd+M exhibited AMH concentrations and peak E(2) levels similar to those observed in HCd.. The improvement of the altered endocrine-metabolic environment of PCOS mothers reduces AMH levels in their daughters, which might reflect a decrease in their follicular mass.

Topics: Adult; Anti-Mullerian Hormone; Birth Weight; Diabetes, Gestational; Female; Fertility Agents, Female; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Infant, Low Birth Weight; Infant, Newborn; Insulin; Leuprolide; Metformin; Ovarian Follicle; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Testosterone; Young Adult

Topics: 17-Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; Adenosine Triphosphate; Aldo-Keto Reductase Family 1 Member C3; Androstenedione; CCAAT-Enhancer-Binding Protein-beta; Diazoxide; Female; Gene Expression Regulation, Enzymologic; Humans; Hydroxyprostaglandin Dehydrogenases; Hyperandrogenism; Hyperinsulinism; Insulin; Leuprolide; Polycystic Ovary Syndrome; Testosterone; Thinness

The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic-hyper-insulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome.

Topics: Adult; Androgens; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Follicle Stimulating Hormone; Glucose Clamp Technique; Gonadotropin-Releasing Hormone; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Leuprolide; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Testosterone

In the syndrome of familial virilization, insulin resistance, and acanthosis nigricans, the interrelationships are not understood. Twin sisters were studied, along with a lesser affected sister and mother. They manifested amenorrhea, hirsutism, masculinization, hypertension, hyperinsulinemia, hypertriglyceridemia, and hyperprolactinemia. Medical therapy with a gonadotropin-releasing hormone agonist plus an antiandrogen resulted in reversal of the hirsutism, yet with preservation of potential fertility. In response to luteinizing hormone (LH) and follicle-stimulating hormone suppression, there was normalization of the serum androgens, but not of the hyperinsulinemia, hypertriglyceridemia, hyperprolactinemia, hypertension, or acanthosis nigricans.. (1) This syndrome may be familial. (2) Medical therapy for the virilization is successful. (3) The hyperandrogenemia is primarily LH dependent and not primarily insulin dependent, although insulin may have an amplification effect. (4) Hyperinsulinemia, hypertriglyceridemia, hyperprolactinemia, and the hypertension are not androgen dependent.

Topics: Acanthosis Nigricans; Adult; Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Dexamethasone; Diseases in Twins; Family Health; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Hyperinsulinism; Hyperlipidemias; Hyperprolactinemia; Hypertension; Insulin Resistance; Leuprolide; Luteinizing Hormone; Male; Pituitary Hormone-Releasing Hormones; Syndrome; Virilism