Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.

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.

Central opioid activity in polycystic ovary syndrome with and without dopaminergic modulation.

It has been hypothesized that brain opioid activity may be decreased in patients with the polycystic ovary syndrome (PCO) and that this decrease may, in part, explain the elevated levels of LH characteristic of the syndrome. We, therefore, examined the LH and PRL responses to naloxone infusions (2 mg/h for 4 h) in seven women with PCO and five weight- and estrogen-matched normal women. The infusions were given both before and after pretreatment with L-dopa-carbidopa (L-DOPA-C) because dopaminergic activity may be decreased in PCO, and dopamine may interact with the brain opioid system. Both PCO patients and normal women had similar responses of serum LH during naloxone treatment; the mean maximum LH responses were 53 +/- 15% (+/- SE) in normal women and 51 +/- 12% in PCO patients (P greater than 0.05). PRL levels were also unaffected by naloxone infusion. After L-DOPA-C pretreatment, baseline LH and PRL levels were unchanged in normal women and PCO patients, and the naloxone-induced LH rise was completely abolished in the normal women. However, in PCO patients, LH increased from 24.7 +/- 4 to 31 +/- 5 mIU/ml, with a mean maximum increase of 112 +/- 33% during naloxone infusion (P less than 0.05). We conclude that 1) brain or central opioid activity is not decreased in PCO; 2) increased central opioid activity does not appear to be responsible for the increased LH levels characteristic of the syndrome; and 3) decreased central dopamine activity and/or the interaction between the dopaminergic and opioid systems may be altered in PCO.

Studies of the nature of 17-hydroxyprogesterone hyperresonsiveness to gonadotropin-releasing hormone agonist challenge in functional ovarian hyperandrogenism.

Plasma 17-hydroxyprogesterone (17PROG) hyperresponsiveness to GnRH agonist (nafarelin) testing is typical of polycystic ovary syndrome and other functional ovarian hyperandrogenism (FOH) that does not meet customary criteria for the diagnosis of polycystic ovary syndrome. We have postulated that this results from abnormal regulation of androgen secretion. Whether this dysregulation is the result of a normal physiological response to ovarian hyperstimulation or escape from down-regulation of steroidogenesis is unknown. To distinguish between these possibilities, we have analyzed the ovarian steroid responses to nafarelin for the apparent efficiency of the steroidogenic steps and the apparent dose-response relationships between blood LH and steroid levels. We compared normal women (n = 18) with three groups of hyperandrogenic women (n = 15-19/group): patients with 17PROG hyperresponsiveness with or without elevated LH levels (type 1 and type 2 FOH, respectively) and patients with normal 17PROG responses to nafarelin (nafarelin negative). Subjects were pretreated with dexamethasone to suppress coincidental adrenal contributions to plasma steroid levels. The pattern of steroid secretion was similarly abnormal in both types of FOH, with the high LH group having generally more severe abnormalities in the levels of steroid intermediates. Baseline 17PROG and 17-hydroxypregnenolone and the ratio of 17PROG to androstenedione (AD) were increased (P < 0.05). In addition, the apparent slope of the 17PROG response to LH was significantly increased. Baseline levels of both AD and dehydroepiandrosterone and the AD response to nafarelin were increased, yet the ratio of peak minus baseline (delta) AD/delta 17PROG (another index of 17,20-lyase activity) was subnormal in FOH. The apparent slope of the testosterone (T) response to LH was significantly increased, and indexes of aromatase activity [estradiol (E2)/T and delta estradiol/delta T] were significantly decreased. Nafarelin stimulated plasma E2 in all groups to rise along an apparently similar LH-E2 dose-response slope. We interpret these results as indicating that FOH patients have generalized overactivity of thecal steroidogenesis, but nevertheless compensate so as to maintain a normal dose-response relationship between blood levels of LH and E2. FOH patients, whether they have LH excess or not, seen to form excessive 17PROG and incompletely dampen (down-regulate) thecal cell 17PROG, AD, and T secretion in response to LH stimulation. 17PROG hyperresponsiveness to nafarelin seems to be prominent both because it is formed in excess and because 17,20-lyase efficiency is rate limiting. The T elevation seems to arise mainly from overactive steroidogenesis, but also partly from an additional functional decrease in aromatase efficiency, which is secondary to negative feedback by the substrate-driven tendency toward estrogen excess.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute hormonal responses to the gonadotropin releasing hormone agonist leuprolide: dose-response studies and comparison to nafarelin--a clinical research center study.

The hormonal responses to single subcutaneous injection of the GnRH agonist nafarelin have been shown to have considerable potential as a diagnostic test in a number of settings. Since nafarelin injection is no longer produced, studies were conducted to determine the dosage of leuprolide that would yield equivalent responses. Nafarelin 100 micrograms stimulates LH and FSH for 24 h, releasing about 7-fold more gonadotropin than this dose of natural GnRH, which accounts for its ability to elicit gonadal steroid responses. Normal adult men and women were randomized to receive leuprolide doses of 0.1, 1.0, or 10 micrograms/kg; a study extension evaluated doses up to 20 micrograms/kg in men. The responses of LH, FSH, testosterone, and estradiol were monitored for 24 h, and the data were compared to those previously obtained on nafarelin. Leuprolide dose of 10 micrograms/kg yielded LH responses similar to 1-1.5 micrograms/kg nafarelin. However, this leuprolide dose unexpectedly released less FSH than nafarelin. Nevertheless, the gonadotropin responses were sufficient to elicit equivalent or greater sex steroid responses to leuprolide. These studies also further delineated sex-specific differences in pituitary responsiveness to challenge with GnRH agonists: men had a significantly lower baseline FSH level, greater LH release within the first hour, and lesser secretion of LH and FSH over the 24-h period. These studies indicate that leuprolide in a dosage of 10 micrograms/kg would be expected to be efficacious in testing the pituitary-gonadal axis in men and women.

Ovarian steroidogenic responses to gonadotropin-releasing hormone agonist testing with nafarelin in hirsute women with adrenal responses to adrenocorticotropin suggestive of 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency.

Nonclassical 3 beta-hydroxy-delta 5-steroid dehydrogenase (3 beta-HSD) deficiency type of congenital adrenal hyperplasia has been hypothesized to occur in as many as 10-40% of hirsute women, based on the adrenal steroidogenic responses to ACTH. However, diagnostic criteria for this "late-onset" 3 beta-HSD deficiency are not clearly established. Among 40 successive hyperandrogenic women undergoing evaluation of adrenal steroidogenic responses to ACTH, 8 had responses suggestive of 3 beta-HSD deficiency. Since 3 beta-HSD is present in both the ovary and adrenal, we attempted to document the defect in the ovary by stimulating their ovarian function with a gonadotropin-releasing hormone agonist test using nafarelin (6-D-[2-naphthyl]alanine-gonadotropin-releasing hormone). The eight hirsute women had steroid responses to ACTH suggestive of 3 beta-HSD deficiency, namely, the values of the delta 5-steroids, 17-hydroxypregnenolone and dehydroepiandrosterone, 30 and 60 min after ACTH in each hirsute woman were greater than 2 SD above the normal mean. Seven of the eight hirsute women had at least one elevated delta 5/delta 4-steroid ratio; however, only three of the hirsute women had two abnormal ratios. Furthermore, the response of the delta 4-steroid androstenedione and the ratio of androstenedione to cortisol after ACTH were significantly increased in the hirsute women, findings not consistent with 3 beta-HSD deficiency. After nafarelin, five and six hirsute patients had elevated values of the delta 4-steroids androstenedione and 17-hydroxyprogesterone, respectively. No patient had an elevated delta 5/delta 4-steroid ratio after nafarelin. Thus, ovarian steroidogenic responses to nafarelin did not support the diagnosis of 3 beta-HSD deficiency. Rather, they are consistent in most cases with polycystic ovary syndrome due to dysregulation of 17-hydroxylase and 17,20-lyase activities. We propose that increased activity of the enzyme P450c17 alpha in the adrenal cortex is responsible for most of what is often termed late-onset 3 beta-HSD deficiency.

Effects of dopamine and metoclopramide in polycystic ovary syndrome.

A relative deficiency in dopamine has been suggested to explain the inappropriate gonadotropin secretion and postulated increased GnRH secretion characteristic of polycystic ovary syndrome (PCO). Previous studies demonstrated an exaggerated decrement in serum LH after large iv doses of dopamine (DA, 4-5 micrograms/kg X min). Normoprolactinemic patients with PCO and weight- and estrogen-matched normal women received iv infusions of DA in two doses (0.5 and 4 micrograms/kg X min). After DA, each subject also received iv metoclopramide (MCP; 10 mg). Serum LH decreased (P less than 0.05) during DA infusion to a similar degree in PCO [23 +/- 3% (+/- SE)] and normal women (20 +/- 2%). In PCO patients, the decrease in LH was similar with both DA doses. Serum PRL and TSH responses to DA were also similar in PCO and normal women. After MCP treatment, serum LH did not change, but serum PRL increased more in PCO (801 +/- 100%) than in normal women (467 +/- 73%; P less than 0.05), as did serum TSH. These data suggest that the sensitivity of LH to DA in patients with PCO is not increased. Further, increased responses of PRL and TSH to MCP may reflect increased dopaminergic activity or, in the case of PRL, the influence of chronic hyperestrogenism.

Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women.

Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency often have a polycystic ovary-like syndrome, consisting of hyperandrogynism, infertility, menstrual irregularities, and elevated LH levels. This is generally considered secondary to poor control of the congenital adrenal hyperplasia. However, our experience led us to suspect that ovarian hyperandrogenism occurs even when congenital adrenal hyperplasia is well controlled on glucocorticoid therapy. Therefore, we tested the hypothesis that congenital adrenal virilizing disorders result in ovarian hyperandrogenism. We studied eight women with congenital adrenal virilizing disorders, seven with well controlled classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma removed at 1.7 yr of age. We also studied six women with late-onset 21-hydroxylase deficiency, without signs of congenital virilization. An ovarian source of androgens was assessed after suppressing adrenal function with dexamethasone and then testing pituitary-ovarian function by a GnRH agonist (nafarelin) test. Five women with congenital adrenal virilizing disorders (four with classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma) and one women with late-onset 21-hydroxylase deficiency had ovarian hyperandrogenism as determined by subnormal suppression of free testosterone after dexamethasone and/or by increased 17-hydroxyprogesterone response to nafarelin while on dexamethasone. All women with congenital adrenal virilization and ovarian hyperandrogenism had elevated LH levels after dexamethasone or elevated early LH response to nafarelin, which suggests that LH excess is the cause of their ovarian hyperandrogenism. This was not the case for the late-onset 21-hydroxylase-deficient woman. Our data are compatible with the hypothesis that congenital adrenal virilization programs the hypothalamic-pituitary axis for hypersecretion of LH at puberty. This is postulated to frequently cause ovarian hyperandrogenism even when adrenal androgen excess is subsequently controlled by glucocorticoid therapy.

Defects in beta-cell function in functional ovarian hyperandrogenism.

Previous studies have shown that hyperinsulinism is associated with hyperandrogenism in patients with the polycystic ovary syndrome, a form of functional ovarian hyperandrogenism (FOH). Although many studies have documented insulin resistance and hyperinsulinemia in polycystic ovary syndrome, the relative roles of insulin secretion and clearance in the pathogenesis of the hyperinsulinism remain uncertain. In this study, using individually derived C-peptide kinetic parameters, insulin secretion rates were calculated directly from plasma C-peptide concentrations in 10 patients with FOH and 7 weight-matched control subjects. All subjects were studied during a 24-h period when they ate a standardized diet consisting of 3 mixed meals. On a separate occasion, insulin sensitivity was calculated during a hyperinsulinemic euglycemic clamp. Although glucose concentrations in both groups were within the normal range, the FOH group had higher basal (P < 0.01) and 24-h insulin (P < 0.04) concentrations. The increased insulin concentrations reflected both a reduced clearance (P < 0.02) and an increased secretion of insulin. Basal insulin secretion rates were significantly increased (P < 0.04) in the FOH patients. By contrast, their incremental insulin secretory response to meals was markedly reduced. This reduction in the postprandial responses resulted from a reduction in the relative amplitude of meal-related (P < 0.007) secretory pulses, rather than from a reduction in the number of pulses present. Insulin sensitivity was also lower in those with FOH. Thus, women with FOH have significantly higher basal insulin secretory rates and attenuated secretory responses to meals. These secretory patterns resemble those of noninsulin-dependent diabetes mellitus more than they do those of simple obesity.

Response to challenge with gonadotropin-releasing hormone agonist in a mother and her two sons with a constitutively activating mutation of the luteinizing hormone receptor--a clinical research center study.

The pituitary-gonadal axis was evaluated in a mother after two of her sons with familial male-limited pseudoprecocious puberty were found to have a constitutively activating mutation of the LH receptor (LHR). Genotyping demonstrated that all showed a mutation in one of the two alleles, a substitution of Gly for Asp578 in the sixth transmembrane segment of the LHR. Ovarian function was normal in the 36-yr-old mother as assessed by LH dynamics and FSH and androgen levels throughout the menstrual cycle. Hormonal responses to acute GnRH agonist (nafarelin) challenge, chronic GnRH agonist administration, and dexamethasone were also normal. Studies of the boys upon presentation at 2.4 and 3.5 yr of age revealed that acute LH responses to nafarelin were in the hypogonadotropic range, and the FSH responses were prepubertal despite the presence of late pubertal testosterone blood levels. Upon the inception of true puberty at 11 yr of age in the older brother, gonadotropin responses normalized for the state of development. The data show that this activating LHR mutation does not cause functional ovarian hyperandrogenism and causes only incomplete pubertal activation of Leydig cells. The results are compatible with relatively low constitutive activity associated with this structural abnormality of LHR.

Menstrual disorders in adolescence.

Current concepts of normal and pathologic puberty have been reviewed because menstrual abnormalities are usually due to abnormal maturation of the reproductive endocrine system. Schema are presented for the initial evaluation of patients with amenorrhea or oligomenorrhea based upon whether they are hypoestrogenic or estrogenized. The role of the bone age in the differential diagnosis of delayed puberty is emphasized. The differential diagnosis and management of excessive genital bleeding and dysmenorrhea in adolescence are given.

Transmission disequilibrium of maternally-inherited CTLA-4 microsatellite alleles in idiopathic recurrent miscarriage.

To elucidate the mechanisms that facilitate tolerance at the maternal-fetal interface, we are investigating the role of genes that are involved in peripheral self-tolerance in couples with idiopathic recurrent miscarriage. CTLA-4 is a negative regulator of T-cell proliferation and has been associated with human autoimmune disease. An AT(n) polymorphism in the 3'-untranslated region (UTR) of the human gene results in AT stretches that vary in length from 16 to 46 bp. We hypothesized that long stretches of AT repeats would result in mRNA instability, and reduced fetal survival in humans. We examined the transmission of AT(n) alleles in 60 couples with a history of > or = 3 unexplained spontaneous abortions to their 51liveborn children and 10 abortuses. The shorter allele was transmitted from heterozygous mothers to 26 of 35 liveborn children (chi2 = 8.3, P = 0.0040) and to three of nine aborted fetuses (chi2 = 1.0, P = 0.317). The shorter allele was transmitted from heterozygous fathers to 15 of 32 liveborn children (chi2 =0.12, P=0.726) and to five of eight aborted fetuses (chi2 = 0.5, P = 0.480). Furthermore, liveborn fetuses who inherited smaller alleles were more likely to represent the first successful pregnancy than liveborn fetuses who inherited larger maternal alleles (Pexact = 0.044) and fetuses of first pregnancies that inherited the smaller allele were significantly more likely to survive to term (Pexact = 0.0086). The preferential transmission of maternally-inherited shorter alleles to liveborn children, but random transmission of paternally-inherited alleles, suggests that CTLA-4 may be imprinted in humans and that this gene may play a role in inducing or maintaining tolerance at the maternal-fetal interface.

Gonadotropin-releasing hormone agonist as a probe for the pathogenesis and diagnosis of ovarian hyperandrogenism.

We have found that women with typical polycystic ovary syndrome have supranormal plasma 17-hydroxyprogesterone responses to a 100-micrograms test dose of the gonadotropin-releasing hormone agonist nafarelin without evidence of hindered estrogen secretion. To understand the basis of this response, we computed the apparent efficiency of the steps in steroid biosynthesis from the pattern of plasma steroids in response to nafarelin. The proximate cause appears to be excessive 17 alpha-hydroxylase activity and high, yet partially down-regulated, 17,20-lyase activity in the delta 4-pathway. These results suggest that this pattern of steroid secretion results from abnormal regulation (dysregulation) of these activities, possibly involving the enzyme cytochrome P450c17. To determine the usefulness of nafarelin testing for the diagnosis of ovarian hyperandrogenism, we then prospectively studied 40 hyperandrogenic women. The plasma 17-PROG response to nafarelin was supranormal in 58% of the women. The responses of 17-PROG to nafarelin and free testosterone to dexamethasone correlated well and were concordant in approximately 85% of cases. Baseline serum luteinizing hormone concentration was elevated in only 48% of cases. To understand ovarian structure-function relationships, we studied another 20 consecutive hyperandrogenic women. Among seven women with polycystic ovaries, five had an elevated LH level, and four of these five (80%) had an elevated 17-PROG response to nafarelin. Conversely, about half of patients with the PCOS-like disorder of ovarian function did not have polycystic ovaries. Ovarian stromal area, but not LH levels, correlated significantly (r = 0.45) with the 17-PROG response to nafarelin. Thus, both stromal hyperplasia and dysregulation of steroidogenesis seem to be manifestations of abnormal intraovarian regulation of cell growth and function. We conclude that a PCOS-like disorder of ovarian function in response to nafarelin testing is found in approximately half of hyperandrogenic women. The pathogenetic implication of our results is that abnormal intraovarian modulation of LH action seems to be a major factor in ovarian hyperandrogenism. The diagnostic implication of our data is that ovarian androgen excess will often be missed by use of common diagnostic criteria for PCOS.

Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women.

Thirty-five women who had undergone a natural or surgical menopause were randomized to receive either 0.625 mg of conjugated estrogen to be ingested for 25 days each month or 150 mg of depo-medroxyprogesterone acetate intramuscularly every three months. Plasma lipids were determined before and after one year of therapy. Serum androgens were measured before and after six months of therapy. Conjugated estrogens and depo-medroxyprogesterone acetate had similar effects on plasma lipids. Cholesterol was decreased (P less than .02 for conjugated estrogen therapy and P less than .01 for depo-medroxyprogesterone acetate therapy), as was low-density lipoprotein cholesterol (P less than .02 for conjugated estrogen and P less than .05 for depo-medroxyprogesterone acetate). Conjugated estrogens also significantly increased high-density lipoprotein cholesterol (P less than .02). High-density lipoprotein cholesterol levels were unchanged after depo-medroxyprogesterone acetate therapy. Serum androgens were generally unchanged after depo-medroxyprogesterone acetate or conjugated estrogen therapy. The data from this study suggest that long-term conjugated estrogen and depo-medroxyprogesterone acetate treatment have similar effects on lipid and androgen levels except that high-density lipoprotein cholesterol was not significantly increased by depo-medroxyprogesterone acetate.

Peripheral dopamine metabolism in polycystic ovary syndrome.

It has been proposed that a relative dopamine deficiency or an increased sensitivity of the gonadotrope to dopamine may explain the elevated luteinizing hormone (LH) levels characteristic of polycystic ovary syndrome. To study one aspect of this issue, that of peripheral dopamine metabolism in polycystic ovary syndrome, we measured the conversion of dopamine to norepinephrine after intravenous dopamine infusions in women with polycystic ovary syndrome and in matched controls. In addition, we measured urinary metabolites of dopamine and norepinephrine, which reflect in part central catecholamine turnover, after daily ingestion of L-dopa with carbidopa, which increases brain dopamine levels. After dopamine infusion in women with polycystic ovary syndrome and in matched controls, steady state levels of plasma dopamine, norepinephrine, and the ratio of dopamine/norepinephrine were similar in the two groups. Similarly, urinary metabolites of dopamine, norepinephrine, and their ratios were not different in patients and controls after L-dopa with carbidopa. We suggest that no major alterations in dopamine metabolism exist in these patients with polycystic ovary syndrome.

Identification of seminiferous tubule aberrations and a low incidence of testicular microliths associated with the development of azoospermia.

OBJECTIVE: To evaluate the use of percutaneous testicular sperm aspiration in the assessment of azoospermia and its association with seminiferous tubule microliths. DESIGN: Case report. SETTING: Tertiary care fertility center in a university hospital. PATIENT(S): Male undergoing infertility evaluation. INTERVENTION(S): Testicular biopsy and percutaneous testicular aspiration. MAIN OUTCOME MEASURE(S): Serum hormone analysis, sperm concentration in semen, spermatogenesis in samples from testicular biopsies and aspirations, and microlith composition. RESULT(S): A patient presented for infertility evaluation with a history of severe oligospermia that progressed to azoospermia. The serum testosterone concentration (357 ng/dL) and LH concentration (9.2 mIU/mL) were normal and the serum FSH concentration (18.3 mIU/mL) was elevated. Testicular biopsy results indicated spermatogenic hypoplasia with limited spermatozoa. Seminiferous tubules obtained by percutaneous testicular aspiration were structurally aberrant, with multiple diverticula. Microliths averaging 120 microm in diameter were observed within and blocking the seminiferous tubules. The microliths were composed of calcium phosphate (hydroxyapatite) in both the core and peripheral regions. Electron microscopy revealed a high degree of collagen-like material within the peripheral zone. CONCLUSION(S): The presence of seminiferous tubule microliths is associated with the development of azoospermia. In patients with a low incidence of seminiferous tubule microliths and aberrant seminiferous tubule architecture, percutaneous testicular aspiration may provide a diagnostic advantage over testicular biopsy.

Correlation of transabdominal and transvaginal ultrasound measurements of follicle size and number with laparoscopic findings for in vitro fertilization.

This paper compared the use of a transvaginal scanning approach with the conventional transabdominal scanning method. In study I, 15 patients with previous suboptimal abdominal ultrasounds were evaluated in subsequent cycles with both the transabdominal and the transvaginal techniques. With the transvaginal method, improvement was observed in 13 patients (87%). Study II compared both the transabdominal and transvaginal ultrasound measurements of follicle number and size with surgical findings. A high correlation (r = 0.914, P less than 0.001) was demonstrated between the number of follicles visualized by transvaginal sonogram and the number of follicles aspirated. A significant correlation (r = 0.639, P less than 0.001) was also observed between follicular fluid volume and the mean ultrasound follicle diameter determined transvaginally.

Correlation of the bioactivity of luteinizing hormone in follicular fluid with oocyte maturity in the spontaneous cycle.

This study was done to measure the bioactivity of luteinizing hormone (LH) in follicular fluid (FF) and to correlate this and other hormonal values with oocyte maturity in the spontaneous cycle. Twenty follicles (greater than 18 mm) from 18 ovulatory patients were obtained, and FF, according to oocyte maturity, was divided into three groups (I to III) of increasing maturity. FF progesterone correlated with maturity and was highest (P less than 0.01) in group III; estradiol, prolactin, and follicle-stimulating hormone were similar in the three groups. Immunoreactive LH was similar in groups I and II but was highest (30.5 +/- 7 mIU/ml) in group III (P less than 0.02). Bioactive (bio) LH was much higher in group III follicles (1307 +/- 387 mIU/ml); the bio:immunoreactive LH ratio also increased significantly (P less than 0.05). FF progesterone correlated positively with bio LH (r = 0.89, P less than 0.005) and the bio:immunoreactive LH ratio (r = 0.9, P less than 0.001); immunoreactive LH did not correlate. These data suggest that bioactivity of LH is an important correlate of oocyte maturity and that local ovarian factors may modulate these concentrations in FF.

Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17 alpha) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17 alpha.

Secretory dynamics of bioactive and immunoreactive prolactin in polycystic ovary syndrome.

To further investigate prolactin (PRL) secretion in polycystic ovary syndrome (PCO), the authors evaluated immunoreactive (immuno) and bioactive (bio) PRL levels in the basal state and in response to provocative testing with intravenous dopamine (DA), metoclopramide (MCP), and gonadotropin-releasing hormone (GnRH), before and after disulfiram. Basal measurements of immuno-PRL, bio-PRL, and the ratio of bio/immuno-PRL were similar in PCO and controls. The immuno-PRL decrement after DA was greater than that of bio-PRL in both groups (P less than 0.05). After MCP, immuno-PRL increased more than bio-PRL in PCO (P less than 0.01), and this immuno-PRL increment was greater than that of controls (P less than 0.05). Bio-PRL and immuno-PRL increased after GnRH in PCO, but not controls, and these responses were inhibited by disulfiram. These data confirm PRL hypersecretion in some women with PCO, which is better expressed by immunoreactivity than bioactivity. Given the assay systems and patients studied, bioactivity

Chlamydia trachomatis is not an important cause of abnormal postcoital tests in ovulating patients.

To examine the role of Chlamydia trachomatis infections of the cervix and abnormal postcoital tests (PCT) in a general infertility clinic, 63 consecutive patients undergoing a midcycle PCT during a routine infertility workup underwent endocervical curettage, and a 10-ml blood sample was obtained. The endocervical tissue was cultured for C. trachomatis; the serum sample was analyzed for chlamydial IgG and IgM antibodies using an indirect microimmunofluorescence assay. A negative titer was considered to be less than or equal to 1:8 dilution for IgG antibodies and less than or equal to 1:32 dilution for IgM antibodies. A good PCT was defined as greater than or equal to 5 motile sperm per high power field (HPF). A poor PCT was defined as less than 2 motile sperm/HPF, and a fair PCT was defined as 2 to 4 motile sperm/HPF. Of the 63 PCTs done, 27 (42.9%) were good, 14 (22.2%) were fair, and 22 (34.9%) were poor. All endocervical tissue cultures for C. trachomatis obtained during PCTs were negative. All IgM chlamydial antibody titers were negative (less than or equal to 1:32 dilution), 55 (87.3%) of the patients having a zero titer. Eleven (17.5%) of the patients had negative IgG chlamydial antibody titers (less than or equal to 1:8 dilution), none of the patients had a 1:16 dilution, and 52 (82.5%) had positive IgG chlamydial antibody titers (greater than or equal to 1:32 dilution). Thus, chlamydial infections of the endocervix are rare and not commonly associated with poor PCTs in this patient population.