Variation of luteinizing hormone and androgens in oligomenorrhoea and its implications for the study of polycystic ovary syndrome.
We measured luteinizing hormone (LH) and androgen concentrations in patients at different phases of the oligomenorrhoeic cycle and compared the results with those of patients with normogonadotrophic amenorrhoea. Several blood samples separated by >/=7 days were obtained from each of 72 patients with oligomenorrhoea and 18 with normogonadotrophic amenorrhoea. The oligomenorrhoeic cycle was divided into five phases: the postmenstrual phase week 1 (day 1-7) and week 2 (day 8-14), the specific oligomenorrhoeic phase (SOP, day 15 after a menstruation to day 21 before the next menstruation), the possibly peri-ovulatory phase (days 21-11 before menstruation) and the premenstrual phase (days 10-1 before menstruation). Samples obtained in the possibly peri-ovulatory phase were excluded. Within individuals LH concentrations were significantly higher during the SOP than during all other phases of the oligomenorrhoeic cycle (paired t-test, P = 0.0001-0.03). In contrast to the other phases of the oligomenorrhoeic cycle, no significant differences in gonadotrophins, androgen or oestradiol concentrations were found between the SOP and normogonadotrophic amenorrhoea. In oligomenorrhoea timing of blood sampling influences the measurement of LH and androgen concentrations, and the accurate interpretation of these measurements requires that the dates of menstruation both before and after the sample is taken should be known. In patients with oligomenorrhoea blood samples should be obtained during the SOP, when the endocrinology is comparable with that of normogonadotrophic amenorrhoea. (+info)
Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study. (+info)
Endocrine features of polycystic ovary syndrome in a random population sample of 14-16 year old adolescents.
Hospital based studies have shown that oligomenorrhoeic adolescents have high luteinizing hormone (LH) and androgen concentrations, endocrine signs of polycystic ovary syndrome (PCOS). The prevalence of these abnormalities in an unselected population of adolescents is not known. We determined LH, follicle stimulating hormone (FSH), androstenedione, testosterone, dehydroepiandrosterone sulphate (DHEAS), oestradiol and prolactin concentrations in unselected population samples of adolescents with oligomenorrhoea, secondary amenorrhoea and regular menstrual cycles. A total of 2248 white, west European adolescents, aged 15.3 +/- 0.6 (mean +/- SD) years, participated. Blood was taken from 107 adolescents with regular menstrual cycles, 52 with oligomenorrhoea and four with secondary amenorrhoea. Oligomenorrhoeic adolescents had higher mean LH, androstenedione, testosterone, DHEAS and oestradiol concentrations compared with girls with regular menstrual cycles; 57% of the oligomenorrhoeic girls had LH or androgen concentrations above the 95th centile of adolescents with regular menstrual cycles. None of the 52 oligomenorrhoeic girls and only one of four girls with secondary amenorrhoea had a hypogonadotrophic endocrine pattern. The present study and available literature support the view that oligomenorrhoea in adolescents is not a stage in the physiological maturation of the hypothalamic pituitary-ovarian axis but an early sign of PCOS associated with subfertility. Physicians should consider endocrine evaluation before reassuring oligomenorrhoeic girls or prescribing oral contraceptives to these girls. (+info)
Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea.
Hyperinsulinaemic insulin resistance is commonly associated with hyperandrogenaemia, and menstrual dysfunction. The aim of this study was to examine the effects of the insulin sensitizing drug, metformin, on ovarian function, follicular growth, and ovulation rate in obese women with oligomenorrhoea. Twenty obese subjects with oligomenorrhoea [polycystic ovarian syndrome; (PCOS)] were observed longitudinally for 3 weeks prior to and for 8 weeks during treatment with metformin (850 mg twice per day). Fifteen patients completed the study. The frequency of ovulation was significantly higher during treatment than before treatment (P = 0.003). A significant decline in both testosterone and luteinizing hormone concentrations was recorded within 1 week of commencing treatment. Patients with elevated pretreatment testosterone concentrations showed the most marked increase in ovulation rate (P < 0.005), and significant reductions in circulating testosterone from 1.02 to 0.54 ng/ml (P < 0.005) after only 1 week of treatment. However, the sub-group with raised fasting insulin showed less marked changes, and the sub-group with normal testosterone concentrations showed no effect of treatment. Metformin had a rapid effect upon the abnormal ovarian function in hyperandrogenic women with PCOS, correcting the disordered ovarian steroid metabolism and ovulation rate; however, there appeared to be no effect in cases where the circulating androgen concentration was normal. (+info)
Women with polycystic ovary syndrome gain regular menstrual cycles when ageing.
The aim of this study was to investigate if previously oligo- or amenorrhoeic polycystic ovary syndrome (PCOS) patients gain regular menstrual cycles when ageing. Women registered as having PCOS, based on the combination of oligo- or amenorrhoea and an increased LH concentration, were invited by letter to participate in a questionnaire by telephone. In this questionnaire we asked for the prevalent menstrual cycle pattern, which we scored in regular cycles (persistently shorter than 6 weeks) or irregular cycles (longer than 6 weeks). We interviewed 346 patients of 30 years and older, and excluded 141 from analysis mainly because of the use of oral contraceptives. The remaining 205 patients showed a highly significant linear trend (P < 0.001) for a shorter menstrual cycle length with increasing age. Logistic regression analysis for body mass index, weight loss, hirsutism, previous treatment with clomiphene citrate or gonadotrophins, previous pregnancy, ethnic origin and smoking showed no influence on the effect of age on the regularity of the menstrual cycle. We conclude that the development of a new balance in the polycystic ovary, solely caused by follicle loss through the process of ovarian ageing, can explain the occurrence of regular cycles in older patients with PCOS. (+info)
Clinical presentation of PCOS following development of an insulinoma: case report.
A 24 year old woman presented with a prolonged clinical history of fasting and exertional hypoglycaemia, and was subsequently diagnosed with an insulinoma. Concurrent symptoms of oligomenorrhoea and hyperandrogenism of similar duration were noted. Biochemically, hyperinsulinaemia was observed in association with a raised serum luteinizing hormone (LH), raised testosterone and androstendione concentrations. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS) but minimal change was observed in the ovarian ultrasound appearances. This case demonstrates the role of insulin in mediating the hypersecretion of both LH and androgens in women with polycystic ovaries. We suggest that hyperinsulinaemia converted occult 'polycystic ovaries' to become clinically manifest as 'polycystic ovary syndrome'. This paradigm has clear implications for women with insulin dependent diabetes mellitus who presumably have systemic hyperinsulinaemia. (+info)
Are synchronised swimmers at risk of amenorrhoea?
OBJECTIVE: Synchronised swimming is a sport that shares certain characteristics with other aesthetically pleasing sports such as gymnastics and dance. The purpose of this investigation was to ascertain whether the highest ranked synchronised swimmers in the United Kingdom experience menstrual abnormalities, a common medical problem seen in these related activities. METHODS: Twenty three members of the Great Britain synchronised swimming squad completed a questionnaire on menstrual history. Body composition and VO(2)MAX were measured in the laboratory during regular physiological screening. RESULTS: Three of the 23 subjects were oligomenorrhoeic and none were amenorrhoeic. All were postmenarchal. Mean estimated body fat percentage was 23%, and mean VO(2)MAX was 47.2 ml/kg/min. CONCLUSIONS: It appears that synchronised swimmers in the United Kingdom are relatively protected from menstrual disturbances for reasons that cannot be explained in isolation. (+info)
Studies on the metabolic clearance rate and production rate of human luteinizing hormone and on the initial half-time of its subunits in man.
The metabolic clearance rate (MCR) of human luteinizing hormone (hLH) has been determined in 10 normal men, 3 normal women, and in 12 women with ovulatory disorders resulting in oligomenorrhea or amenorrhea. The MCR was determined by the constant infusion technique using either iodinated or unlabeled highly purified hLH, and these results were compared to MCR determined by using crude pituitary preparations containing both follicle-stimulating hormone and hLH. Both preparations produced essentially similar results for the MCR of hLH and virtually identical results were obtained when complete or incomplete immunoprecipitation of the infused material was achieved. The MCR/body surface area of hLH was significantly greater in normal men (25.6 plus or minus 3.6 ml/min-m-2) than in normal premenopausal (19.2 plus or minus 0.9 ml/min-m-2) or postmenopausal women (17.4 plus or minus 1.9 ml/min-m-2). No difference was noted in the MCR of hLH in women with oligomenorrhea or amenorrhea. Production rates (PRs) were calculated by using a pituitary standard, the values being 85.1 plus or minus 21.5 IU/24 h in normal men, 39.9 plus or minus 12.6 IU/24 h in normal premenopausal women, and 294.6 plus or minus 61.9 IU/24 h in normal postmenopausal women. The initial half-times of disappearance of the alpha- and beta-subunits of hLH were measured in two normal men and found to be 15-18 min, respectively. The half-time of intact hLH was twice as great. (+info)