The recent discovery of the obese (ob) gene has provided new insight into the mechanism which controls body fat mass. Leptin, a product of the ob gene, serves as the link between fat and the brain. This protein, by acting at the level of the hypothalamus, decreases food intake and increases energy expenditure. Animals that lack leptin (ob/ob mice) develop profound obesity and become infertile. Treatment of these animals with leptin reduces food intake and restores normal fertility. Although leptin is important for the control of fat stores in certain species, the role of this substance in the development of human obesity remains obscure. However, it has been speculated that, in humans, obesity is related to leptin resistance. The relationship between fat and reproduction has been recognized for >20 years. This article discusses the relationship between leptin and human reproduction. In particular, recent knowledge about the possible role of leptin in various conditions such as puberty, polycystic ovary syndrome and pregnancy is reviewed. Also, the article discusses the possible role of leptin in ovarian function and the relationship of this protein with gonadal steroids. It is expected that future research will clarify the physiological importance of leptin in human reproductive function. (+info)
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
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OBJECTIVE: NIDDM occurs commonly among women with polycystic ovary syndrome (PCOS). The prevalence and natural history of its precursor, impaired glucose tolerance (IGT), is less well known. The objective of this study was to characterize the prevalence and incidence of glucose intolerance in a large cohort of women with well-characterized PCOS. RESEARCH DESIGN AND METHODS: A total of 122 women with clinical and hormonal evidence of PCOS were recruited from the Medicine, Endocrinology, Gynecology, and Pediatrics Clinics at the University of Chicago. All women had a standard oral glucose tolerance test (OGTT) with measurement of glucose and insulin levels. A subset of 25 women were subsequently restudied with the aim of characterizing the natural history of glucose tolerance in PCOS. RESULTS: Glucose tolerance was abnormal in 55 (45%) of the 122 women: 43 (35%) had IGT and 12 (10%) had NIDDM at the time of initial study. The women with NIDDM differed from those with normal glucose tolerance in that they had a 2.6-fold higher prevalence of first-degree relatives with NIDDM (83 vs. 31%, P < 0.01 by chi 2) and were significantly more obese (BMI 41.0 +/- 2.4 vs. 33.4 +/- 1.1 kg/m2, P < 0.01). For the entire cohort of 122 women, there was a significant correlation between fasting and 2-h glucose concentrations (r = 0.76, P < 0.0001); among the subset with IGT, the fasting glucose concentration was poorly predictive of the 2-h level (r = 0.25, NS). After a mean follow-up of 2.4 +/- 0.3 years (range 0.5-6.3), 25 women had a second OGTT. The glucose concentration at 2 h during the second glucose tolerance test was significantly higher than the 2-h concentration during the first study (161 +/- 9 vs. 139 +/- 6 mg/dl, P < 0.02). CONCLUSIONS: The prevalence of IGT and NIDDM in women with PCOS is substantially higher than expected when compared with age- and weight-matched populations of women without PCOS. The conversion from IGT to NIDDM is accelerated in PCOS. The fasting glucose concentration does not reliably predict the glucose concentration at 2 h after an oral glucose challenge, particularly among those with IGT, the subgroup at highest risk for subsequent development of NIDDM. We conclude that women with PCOS should periodically have an OGTT and must be closely monitored for deterioration in glucose tolerance. (+info)
Dexamethasone supplementation to gonadotropin stimulation for in vitro fertilization in polycystic ovarian disease.
(19/1493)
PURPOSE: This study was conducted to determine whether glucocorticoid supplementation for patients with polycystic ovarian disease during ovulation induction with gonadotropins for in vitro fertilization (IVF) therapy is beneficial. METHODS: Seventy-one cycles of patients undergoing first attempts at IVF, with classical polycystic ovarian disease and hyperandrogenemia, who enrolled in the IVF-embryo transfer program, were evaluated retrospectively. In 20 cycles (20 patients) glucocorticoid supplementation was noted and compared to 51 cycles (51 patients) without glucocorticoid as adrenal androgen suppression. Ovaries were stimulated by gonadotropin releasing hormone agonist, human menopausal gonadotropin, and dexamethasone. Ovarian responsiveness and IVF-embryo transfer outcome were analyzed and included the number of follicles > 17 mm in diameter, serum estradiol concentration on the day of human chorionic gonadotropin administration, number of human chorionic gonadotropin ampoules administered, number of oocytes retrieved, percentage of oocytes fertilized, number of embryos transferred, implantation rate, and number of clinical pregnancies and their outcome. RESULTS: The results showed that the pregnancy rate in patients who received glucocorticoid was 22.1%, compared to 26% in the controls (statistically insignificant). The IVF cycle variables studied revealed no statistically significant differences. CONCLUSIONS: Our observations did not support the notion that adrenal androgen suppression by glucocorticoid, or as an adjuvant therapy, is beneficial to patients with polycystic ovarian disease who enrolled in an IVF-embryo transfer program. (+info)
Leptin, polycystic ovaries and polycystic ovary syndrome.
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As soon as leptin was discovered four years ago, its potential as a player in the polycystic ovary syndrome (PCOS) was explored in a primitive way, though little light was shed on the enigma that is PCOS. As a second wave of leptin research is now available, we review how the expanded role of the cytokine in reproduction might yet impact upon our understanding of PCOS. (+info)
Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome?
(21/1493)
Animal and human studies suggest that leptin modulates hypothalamic-pituitary-gonadal axis functions. Leptin may stimulate gonadotrophin-releasing hormone (GnRH) release from the hypothalamus and luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women, suggesting that leptin probably also regulates the episodic secretion of LH. In some pathological conditions, such as polycystic ovarian syndrome (PCOS), LH-leptin interactions are not known. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin in PCOS patients compared to regularly menstruating women. Six PCOS patients and six normal cycling (NC) women of similar age and body mass index (BMI) were studied. To assess episodic hormone secretion, blood samples were collected at 10-min intervals for 6 h. LH and leptin concentrations were measured in all samples. For pulse analysis the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of copulsatility was employed. LH concentrations were significantly higher in the PCOS group in comparison to NC women, however serum leptin concentrations and leptin pulse characteristics for PCOS patients did not differ from NC women. A strong synchronicity between LH and leptin pulses was observed in NC women; 11 coincident leptin pulses were counted with a phase shift of 0 min (P = 0.027), 18 pulses with a phase shift of -1 (P = 0.025) and 24 pulses with a phase shift of -2 (P = 0.028). PCOS patients also exhibited a synchronicity between LH and leptin pulses but weaker (only 20 of 39 pulses) and with a phase shift greater than in normal women, leptin pulses preceding LH pulses by 20 min (P = 0.0163). These results demonstrate that circulating leptin and LH are synchronized in normal women and patients with PCOS. The real significance of the apparent copulsatility between LH and leptin must be elucidated, as well as the mechanisms that account for the ultradian leptin release. (+info)
Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization.
(22/1493)
Increased androgen concentrations are thought to be detrimental to oocyte quality and reproductive potential. Adjuvant treatment with glucocorticoids has been tried to suppress androgens in women undergoing infertility treatment. In the present study 20 infertile women with polycystic ovary syndrome were prospectively randomized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night, during standard in-vitro fertilization (IVF) treatment. Serum samples for assays of gonadotrophins, steroids and sex hormone-binding globulin (SHBG) were collected before treatment, at down-regulation, and at oocyte retrieval. Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes, the rest according to the clinic's routines. In the placebo group, serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S) did not change between down-regulation and oocyte retrieval, whereas adjuvant prednisolone resulted in a significant decrease. In follicular fluid, adjuvant prednisolone resulted in significantly lower concentrations of DHEA-S as compared to placebo, no other significant differences were found. No significant differences were found in embryo characteristics or pregnancy rates between the groups. (+info)
Is glycosylated haemoglobin a marker of fertility? A follow-up study of first-pregnancy planners.
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We performed a follow-up study of time to pregnancy in a population of first-time pregnancy planners without previous reproductive experience. The objective of this paper is to report and discuss a finding of a strong relationship between glycosylated haemoglobin (HbA1C) and fertility. A total of 165 Danish couples without previous reproductive experience was followed from termination of birth control until pregnancy for a maximum of six menstrual cycles. HbA1C and reproductive hormones were measured at entry. Questionnaire data were collected at entry and once in each cycle during follow-up. The odds ratio (OR) for pregnancy per cycle decreased with increasing concentration of HbA1C (OR per percent HbA1C 0.4, 95% CI 0.2-0.9 for all six cycles and 0.2, 95% CI 0.1-0.5 in the first three cycles). A high concentration of HbA1C was associated with a high concentration of testosterone and a low concentration of inhibin A. No association was found between HbA1C and psychosocial distress. The reduced fertility among women with high HbA1C may be due to an association with subclinical polycystic ovaries as indicated by the hormonal profile. (+info)
The outcome of in-vitro fertilization treatment in women with sonographic evidence of polycystic ovarian morphology.
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This study compared the outcome of a course of up to three cycles of in-vitro fertilization (IVF) treatment in 46 women (97 cycles) who had polycystic ovaries (PCO) seen on ultrasound scan, but who had no clinical symptomatology associated with polycystic ovary syndrome, with that of 145 women (332 cycles) who had normal ovarian morphology on ultrasound examination. All 191 women had normal early follicular phase serum follicle stimulating hormone (FSH) concentrations, were less than 40 years of age and used the long protocol of pituitary suppression with gonadotrophin-releasing hormone agonist therapy. On average, the women with PCO produced more follicles, oocytes and embryos than the women with normal ovaries, but the fertilization, cleavage and miscarriage rates were similar. Adjusted for age, the odds of achieving a pregnancy within three cycles of treatment in a woman with PCO were 69% higher than those of a woman with normal ovaries [odds ratio (OR): 1.69, 95% confidence interval (CI) 0.99-2.90, P = 0.05)] and the odds of achieving a live birth were 82% higher (OR: 1.82, 95% CI 1.05-3.16, P = 0.03). There is, therefore, evidence that outcome of IVF treatment for women with PCO seen on ultrasound examination may be better than that for women with normal ovaries. (+info)