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Objective: The mechanism of dominant follicle selection remains obscure. We have investigated the association between follicle diameter and follicular steroid levels in individual human ovarian follicles throughout the menstrual cycle., Design: Fluid from ovarian follicles (n = 326) was obtained in vivo during surgery from 55 regularly cycling women with proven fertility. Follicles were divided into dominant (diameter >9 mm, n = 45) and non-dominant (diameter < or = 9 mm, n = 281) based on ultrasound measurements., Measurements: Fluid was assayed for oestradiol (E2), androstenedione (AD), and progesterone (P)., Results: Median P and E2 levels were significantly lower (P < 0.0001) and AD levels significantly higher (P = 0.03) in non-dominant as compared to dominant follicles. In non-dominant follicles AD (r = 0.14, P = 0.02), but not P and E2, levels were correlated to follicular diameter, and significant changes in steroid concentrations across the menstrual cycle were absent. In dominant follicles, diameter was positively correlated with P and E2 (P < 0.001) levels, and inversely correlated with AD concentrations (P = 0.01)., Conclusions: Results indicate that (1) intrafollicular oestradiol concentrations rise only in follicles exceeding 9 mm in diameter and correlate with the diameter of these dominant follicles, suggesting that significant increase in aromatase enzyme activity occurs only in the dominant follicle (2) a cycle-independent accumulation of androstenedione with size occurs in non-dominant follicles, and (3) progesterone production occurs in the largest dominant follicles only, suggesting a limited, if any, role for progesterone during follicle development.

Objective: Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome., Patients: Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria., Measurements: Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG., Results: There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients., Conclusions: The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Objective: We evaluated the significance of single serum LH estimates (as assessed by radiometric assay (IRMA) and Leydig cell in-vitro bioassay (BIO)) for the diagnosis of polycystic ovary syndrome (PCOS) in women with infertility and cycle abnormalities., Design: Hormonal and clinical comparisons between subgroups were made based on classification according to (a) rigid clinical and endocrine (excluding LH) characteristics of PCOS, (b) elevated IRMA-LH concentrations, (c) BIO-LH levels. In addition, androgen modulation of LH biopotency was studied in these patients., Patients: Ninety-nine women presenting at our infertility Unit with oligo/amenorrhoea., Measurements and Results: Of the total study group, 35 women were diagnosed positive as PCOS and 42 showed elevated IRMA-LH levels. Only 51% (n = 18) of PCOS patients showed elevated IRMA-LH levels, and in PCOS significantly higher levels of BIO-LH, androstenedione, oestrone, and BIO/IRMA-LH ratios were found as compared to non-PCOS patients. In the group with elevated IRMA-LH only 43% (n = 18) of subjects were diagnosed as PCOS, and no difference in BIO/IRMA-LH ratios was found. With increasing BIO-LH levels the probability of PCOS rises sharply (P < 0.001), whereas this probability is of only marginal significance (P < 0.06) for IRMA-LH. In the total study group a correlation is observed between serum testosterone (T) levels and IRMA-LH (r = 0.47), and BIO-LH (r = 0.51) concentrations. This correlation is absent comparing serum T and BIO/IRMA-LH ratios (r = 0.15)., Conclusions: Results presented in this study indicate that (1) women with infertility and oligo/amenorrhoea classified based on signs of PCOS or IRMA-LH levels, exhibit different clinical and endocrine characteristics, (2) only 51% of PCOS women exhibit elevated IRMA-LH concentrations, and only 43% of women with elevated IRMA-LH were diagnosed as PCOS, (3) IRMA-LH levels are a poor predictor of PCOS, whereas the predictive value of BIO-LH is better, (4) elevated BIO/IRMA-LH ratios in PCOS are dependent on alterations in BIO-LH, rather than IRMA-LH concentrations, and (5) no correlation was observed between serum T levels and BIO/IRMA-LH ratios.

Objective: The aim was to monitor carefully follicular growth arrest in polycystic ovaries by assay of hormones in individual follicles., Design and Patients: Fluid from follicles less than or equal to 10 mm was obtained from ovaries of 16 regularly cycling women between days 1 and 12 of the follicular phase (controls, n = 120 follicles), polycystic ovaries of five women with polycystic ovary syndrome (n = 43), and polycystic ovaries from 14 long-term testosterone treated female to male transsexuals (n = 120)., Measurements: Fluid was assayed for oestradiol, androstenedione, and immunoactive inhibin. Luteinizing hormone, follicle-stimulating hormone, and testosterone levels were estimated in serum., Results: Median serum LH was lower in transsexuals than in controls (P less than 0.05), and in polycystic ovary syndrome (P less than 0.01). Median serum testosterone was not significantly different between polycystic ovary syndrome and transsexuals, and was elevated in both groups as compared to controls (P less than 0.01). Oestradiol was present in all follicles obtained from polycystic ovaries of polycystic and transsexual patients, in which no follicle greater than 10 mm could be detected. In the three groups, between-patient differences in mean oestradiol, androstenedione, inhibin, and androstenedione/oestradiol ratio were significantly larger than expected in view of the variation between follicles within individuals. Taking into account this between-patient difference, no significant differences could be established between the three groups for all endocrine parameters. The percentage of presumed healthy follicles (androstenedione/oestradiol ratio less than or equal to 4) was 12% in controls, 17% in polycystics, and 14% in transsexuals, and was not significantly different between groups., Conclusions: The results may indicate that (1) abnormally high circulating androgen concentrations with or without elevated LH levels disturb the process of selection, and could therefore play a role in the pathogenesis of polycystic ovaries; (2) in polycystic ovaries from polycystic ovary syndrome and transsexual patients, aromatase activity is present in vivo in small antral follicles, and the proportion of presumed healthy follicles is not different from that encountered in normal ovaries; (3) oestradiol levels are not different between non-dominant follicles of normal and polycystic ovaries, suggesting that only enhancement of aromatase activity by FSH may be disrupted in polycystic ovaries, (4) because androstenedione levels are not different comparing follicles of normal and polycystic ovaries, hyperandrogenaemia in the syndrome seems to originate from the abnormally high number of cystic atretic follicles generally observed in polycystic ovaries; (5) marked variation in the endocrine follicular microenvironment within and between-women precludes pooling fluid from several follicles.