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PubMed2002

Overexpression of theca-cell messenger RNA in polycystic ovary syndrome does not correlate with polymorphisms in the cholesterol side-chain cleavage and 17alpha-hydroxylase/C(17-20) lyase promoters.

OBJECTIVE: To determine whether overexpression of CYP17 or CYP11A messenger (m)RNA in theca cells from polycystic ovaries is related to polymorphic regions in the gene promoters that may increase transcription. DESIGN: Case-control study. SETTING: Research institute. PATIENT(S): Fifty-one women with PCOS and 280 regularly cycling controls underwent genotyping. Thecal cells were obtained from 23 women with PCOS and 51 controls. MAIN OUTCOME MEASURE(S): Ovarian tissue was obtained from women with PCOS undergoing wedge resection for treatment of their infertility and from controls undergoing ovariectomy for indications unrelated to the study. Expression of mRNA in theca cells was measured by using competitive reverse transcriptase polymerase chain reaction. Genotype analysis for polymorphisms in the CYP11A and CYP17 promoters was performed by using polymerase chain reaction. RESULT(S): Although expression of CYP11A and CYP17 mRNA was higher in women with PCOS, no significant dose effects of CYP11A or CYP17 alleles were observed with respect to serum testosterone; follicular fluid androstenedione, estradiol, and androstenedione-to-estradiol ratio; or CYP11A or CYP17 mRNA expression. CONCLUSION(S): Overexpression of CYP17 and CYP11A mRNA in theca cells from polycystic ovaries is explained by polymorphic differences in the gene promoters.

Adult↗

PubMed2002

Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome.

OBJECTIVE: Evaluation of clinical and endocrine effects of naltrexone administration in obese women with PCOS. DESIGN: Open, controlled, clinical study. SETTING: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. PATIENT(S): Ten PCOS women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/day) for 6 months. MAIN OUTCOME MEASURE(S): Body mass index and the menstrual cyclicity during naltrexone treatment were assessed. Basal levels of LH, FSH, 17beta-estradiol (E(2)), 17-hydroxyprogesterone, total and free T, androstenedione, dehydroepiandrosterone sulfate, cortisol, sex hormone-binding globulin were evaluated before treatment and every 3 months. Progesterone levels were measured in the luteal phase during the sixth month. Gonadotropin response to GnRH administration (10 microg) and a 75-g oral glucose tolerance test were performed before and every 3 months. RESULT(S): Body mass index significantly decreased from 29.94 +/- 1.04 to 26.07 +/- 0.81 during treatment. The menstrual cyclicity improved in 80% of PCOS women: the mean cycle length was 40-360 days before treatment and ranged between 25 and 120 days and 28-120 days after 3 and 6 months of treatment. Plasma levels of free T, androstenedione, dehydroepiandrosterone sulfate, and cortisol significantly decreased. Fasting glucose-to-insulin ratio improved in women with insulin resistance. CONCLUSION(S): Naltrexone may have a beneficial effect on the clinical and endocrine-metabolic disturbances of obese PCOS women. Whether these effects are the consequences of weight loss or are due to changes in opioidergic tone is debatable.

Adult↗

PubMed2003

Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome.

OBJECTIVE: In women suffering from polycystic ovary syndrome (PCOS), correction of hyperinsulinemia results enhances spontaneous ovulation or alternatively, the responsiveness to ovulation induction agents such as clomiphene citrate (CC). We investigated the effect of rosiglitazone maleate on ovulation induction in overweight and obese, CC-resistant women with PCOS. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Academic reproductive endocrinology clinic. PATIENT(S): Overweight and obese women with clinical and laboratory manifestations of PCOS who desired pregnancy and were resistant to CC. INTERVENTION(S): Twenty-five women were randomized into two treatment groups. Subjects in Group I (n = 12) were randomized to receive rosiglitazone 4 mg b.i.d. with a placebo on cycle days 5-9. Group II (n = 13) was randomized to receive rosiglitazone 4 mg b.i.d. with CC on cycle days 5-9. The duration of the study was 2 months. MAIN OUTCOME MEASURE(S): The primary outcome was ovulation as defined by luteal serum progesterone greater than 5 ng/dL assessed on days 21, 24, and 28 of the cycle. Secondary outcomes were pregnancy and changes in insulin sensitivity, serum lipoproteins, and androgens. RESULT(S): Overall, 14 of 25 (56%) women, who were previously resistant to CC, successfully ovulated. In subjects taking rosiglitazone alone (Group I), 4 of 12 (33%) subjects ovulated compared with 10 of 13 (77%) women randomized to rosiglitazone with CC (Group II) (P=.04, Fisher's exact). One subject in Group I became pregnant, resulting in one uncomplicated live birth; two subjects in Group II conceived, with one successful live birth and one first trimester, spontaneous abortion. For all subjects, fasting insulin declined from 29.4 +/- 13.8 microU/mL to 17.3 +/- 7.8 microU/mL after rosiglitazone (P=.003, paired t-test). Although mean levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) did not decline significantly, sex hormone-binding globulin (SHBG) did increase from 0.7 +/- 0.3 microg/dL to 1.0 +/- 0.3 microg/dL after rosiglitazone therapy (P=.001, paired t test). There was also a decrease in luteinizing hormone (LH) from 9.4 +/- 6.3 mU/mL to 7.2 +/- 3.7 mU/mL (P=.01). Lipoproteins including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides did not change. CONCLUSIONS: Short-term rosiglitazone therapy enhances both spontaneous and clomiphene-induced ovulation in overweight and obese women with PCOS. Rosiglitazone therapy improves insulin sensitivity and decreases hyperandrogenemia primarily through increases in SHBG.

Adolescent↗

PubMed2003

Evaluation of the impact of laparoscopic ovarian drilling on Doppler indices of ovarian stromal blood flow, serum vascular endothelial growth factor, and insulin-like growth factor-1 in women with polycystic ovary syndrome.

OBJECTIVE: To study the serum levels and correlation of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), hormonal profile, and Doppler blood flow changes within the ovarian stroma before and after laparoscopic ovarian drilling (LOD) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective controlled study. SETTING: University teaching hospital. PATIENT(S): Twenty-five women with clomiphene-resistant PCOS (group 1) and 20 women with regular menstrual cycles as a comparison group (group 2). INTERVENTION(S): Laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): Serum levels of VEGF, IGF-1, and Doppler indices of ovarian stromal blood flow. RESULT(S): The serum levels of VEGF, IGF-1, T, and LH were significantly higher in group 1 before LOD than in group 2. The Doppler indices (pulsatility index and resistance index) of ovarian stromal blood flow were also significantly lower in group 1 before LOD than in group 2. The serum levels of VEGF, T, and LH were significantly reduced in group 1 after LOD compared with in group 1 before LOD. Doppler indices (pulsatility index and resistance index) of ovarian stromal blood flow were significantly increased after LOD. The VEGF levels before LOD were positively correlated with IGF-1, LH, and T. After LOD, the VEGF levels were positively correlated with LH and T. CONCLUSION(S): Higher serum levels of VEGF and IGF-1 may explain the increased vascularity that was demonstrated by Doppler blood flow measurements in PCOS. Laparoscopic ovarian drilling reduced serum VEGF, IGF-1, T, and LH and reduced ovarian blood flow velocities, which may explain the reduction of ovarian hyperstimulation syndrome in women with PCOS after LOD.

Angiogenesis Inducing Agents↗

PubMed2003

Troglitazone decreases adrenal androgen levels in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether amelioration of insulin resistance in polycystic ovary syndrome (PCOS) with the insulin sensitizer troglitazone (TGZ) decreases circulating adrenal androgens (AAs), as reflected by DHEAS levels. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: Multicenter study. SUBJECT(S): Three-hundred five women with PCOS. INTERVENTION(S): Subjects were randomly assigned to receive either placebo (PBO; n = 73) or TGZ in doses of 150 mg/day (TGZ-150; n = 78), 300 mg/day (TGZ-300; n = 77), or 600 mg/day (TGZ-600; n = 77) for 20 weeks. Blood was sampled before (week 0) and at week 20 of treatment. MAIN OUTCOME MEASURE(S): DHEAS, insulin, and glucose levels were determined in the blood samples. RESULT(S): There were no differences in age, body mass, or racial composition among the groups. Our results indicate that basal insulin declined in a dose-related fashion. Likewise, TGZ administration caused a dose-related decrease in DHEAS levels. To detect extreme effects, we subsequently subdivided patients receiving PBO or TGZ-600 into tertiles according to initial DHEAS levels. Patients receiving PBO in the lowest (n = 27) and highest (n = 22) DHEAS tertiles experienced a 16.8% +/- 62.0% and a -11.1% +/- 17.4% change in DHEAS levels during the study, respectively. Alternatively, patients with PCOS receiving TGZ-600 in both the lowest (n = 29) and the highest (n = 23) DHEAS tertiles experienced a drop in DHEAS levels (-18.7% +/- 27.2% and -26.4% +/- 17.2%, respectively), a significant difference from PBO. CONCLUSION(S): In conclusion, improving the insulin resistance-related hyperinsulinemia of PCOS with TGZ results in a decrease in DHEAS levels, regardless of initial DHEAS level. Whether the observed suppression is the direct result of decreased insulin levels or whether it reflects other direct and indirect effects of TGZ remains to be determined.

Adrenal Glands↗

PubMed2003

Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles.

OBJECTIVE: To examine whether follicle loss due to ovarian aging is responsible for the occurrence of regular menstrual cycles in aging women with polycystic ovary syndrome (PCOS), the size of the FSH-sensitive follicle cohort was estimated by the exogenous follicle-stimulating hormone ovarian reserve test (EFORT) and related to the follicle count as measured by ultrasound. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENT(S): Twenty-seven aging women with PCOS (35.8-49.4 years): 20 with regular menstrual cycles and 7 with oligomenorrhea or amenorrhea. INTERVENTION(S): EFORT and transvaginal ultrasound. MAIN OUTCOME MEASURE(S): Baseline (cycle day 2, 3, or 4) FSH, androstenedione (A), T, E(2), and inhibin B levels, the E(2) and inhibin B increment after the EFORT, and the follicle count. RESULT(S): After correction for the body mass index (BMI), the inhibin B increment was higher in the irregular menstrual group, but the E(2) increment did not differ significantly between the two groups. Ultrasound showed a median follicle count of 8.5 (4.0-18.0) in women with regular menstrual cycles (n = 16), compared with 18.0 (8.0-35.0) in irregularly menstruating women (n = 7). The follicle count was significantly correlated to the FSH-induced E(2) increment (r = 0.656) as well as to the inhibin B increment (r = 0.654). The regularly menstruating group was significantly older, had a higher basal FSH concentration, and had lower androgens than the irregularly menstruating group. CONCLUSION(S): The smaller follicle count, the older age, the higher FSH concentration, and the lower FSH-induced inhibin B increment found in women with PCOS and a regular menstrual cycle confirm that a decrease in the size of the follicle cohort due to ovarian aging is largely responsible for the regular menstrual cycles in aging PCOS women.

Adult↗

PubMed2003

Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome.

OBJECTIVE: To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Seventy-eight infertile women undergoing IVF-embryo transfer. INTERVENTION(S): The subjects underwent blood sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES: Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes. RESULT(S): The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters. CONCLUSION(S): The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.

Adult↗

PubMed2003

Familial associations in women with polycystic ovary syndrome.

OBJECTIVE: To confirm whether there was a familial association between polycystic ovary syndrome (PCOS) and thromboembolic disease, ovarian or breast cancer, diabetes, and heart disease. DESIGN: Cross-sectional study. SETTING: A university hospital in the United Kingdom. PATIENT(S): Two hundred and seventeen women with and without PCOS under the care of the same consultant gynecologist at a teaching hospital. INTERVENTION(S): Questionnaire survey. MAIN OUTCOME MEASURE(S): Prevalence of a personal or positive family history of thromboembolism, ovarian cancer, breast cancer, diabetes, and heart attacks. RESULT(S): In an analysis of the replies from 41 women with PCOS and 66 controls, we found a statistically significant positive family history of breast cancer and heart attacks among women with PCOS. There was no statistically significant difference in the mean age, ethnic origin, or prevalence of a family history of other diseases. CONCLUSION(S): Our results show a positive association between polycystic ovary syndrome and a family history of breast cancer and heart disease. These associations may be genetic in origin, or secondary to a complex interplay of genetic, intrauterine, and environmental factors. More studies are required to confirm these findings and determine the factors that explain these associations.

Adult↗

PubMed2003

GnRH antagonists for treatment of polycystic ovarian syndrome.

To review treatment options for women with polycystic ovary syndrome (PCOS) seeking relief from infertility. Review article and case studies. Treatment options for women with PCOS include lifestyle modification, treatment with insulin-sensitizing agents, ovulation induction with clomiphene citrate (CC), FSH preparations, and possibly, GnRH antagonists. The GnRH antagonists provide a new treatment option for women with PCOS. When the goal is to restore normal ovulation, the use of GnRH antagonists is limited to the prevention of LH surges. When undertaking controlled ovarian hyperstimulation (COH) in women with PCOS, a GnRH antagonist protocol should be the protocol of choice.

Female↗

PubMed2003

Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the expression of steroid hormone receptors, proteins related to apoptosis, and cell proliferation in endometria from women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Eight women with PCOS and 12 fertile healthy women of similar age to those with PCOS. INTERVENTION(S): Endometrial samples were obtained from women with PCOS (PCOSE) and normal (NE) women during the proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies (immunohistochemistry and reverse transcription-polymerase chain reaction) and DNA fragmentation [TdT-mediated dUTP nick end labeling (TUNEL)]. RESULT(S): In stroma, protein expression of estrogen receptor alpha, Bcl-2, and Bax was higher in PCOSE than in NE; epithelial cells had a greater expression of androgen receptor in the nucleus and a lower expression in the cytoplasm of PCOSE. Cell proliferation was higher in the epithelia of NE, while the expression of caspase-3 and DNA fragmentation was similar in both groups. The bax mRNA expression was higher in PCOSE, and bcl-2 mRNA expression was similar between groups. A higher bcl-2/bax relative ratio in PCOSE was observed. CONCLUSION(S): An alternating expression of proteins related to cell survival in endometria from PCOSE may potentially be associated with the disruption of their endometrial cell cycle.

Adult↗

PubMed1992

The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins.

OBJECTIVE: To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) in women with refractory polycystic ovarian syndrome (PCOS). DESIGN: Retrospective case series with an age-matched control group. SETTING: Ovulation induction and IVF programs in a tertiary referral center. PATIENTS AND INTERVENTIONS: Nine patients with PCOS who failed standard ovulation induction treatment (clomiphene citrate plus greater than or equal to 6 ovulatory human menopausal gonadotropin [hMG] cycles) underwent 19 cycles of IVF-ET. Forty age-matched tubal factor patients who completed 40 cycles of IVF-ET served as a control group. OUTCOME MEASURES: Demographic features and IVF-ET cycle characteristics were compared using Student's t-test and Fisher's exact test. RESULTS: Cycles of IVF-ET in patients with PCOS were associated with higher estradiol levels (5,222 versus 4,009 pmol/L), lower hMG requirements (15.8 versus 19.6 vials), greater numbers of oocytes (7.6 versus 5.6), and lower fertilization rates (56% versus 75%) compared with tubal factor cycles (P less than 0.05). However, the number of embryos transferred (3.9 versus 4.0) and the clinical pregnancy rate per embryo transfer (24% versus 25%) did not differ significantly between the two groups. CONCLUSION: These results suggest that conception failure after six or more ovulatory hMG cycles in patients with PCOS does not adversely affect subsequent IVF performance.

Adult↗

PubMed1992

Polycystic ovaries in patients with hypogonadotropic hypogonadism: similarity of ovarian response to gonadotropin stimulation in patients with polycystic ovarian syndrome.

OBJECTIVE: To characterize the ovarian response in patients with isolated hypogonadotropic hypogonadism with ultrasound (US) findings of polycystic ovaries (PCO). DESIGN: Twenty-seven treatment cycles in patients with hypogonadotropic hypogonadism and US findings of normal ovaries were compared with 31 cycles in patients with hypogonadotropic hypogonadism and US-diagnosed PCO. Forty-one cycles in the hypogonadotropic hypogonadism and US-diagnosed PCO were compared with 59 cycles of patients with polycystic ovarian syndrome (PCOS) to examine pattern of response after ovulation induction. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic patients in whom 10 had US findings of PCO and 13 patients with PCOS. MAIN OUTCOME MEASURE: Serum estradiol (E2) concentration, number of leading follicles on US, cancellation, and pregnancy rate. RESULTS: Hypogonadotropic patients with US-diagnosed PCO had higher baseline ovarian volume (P less than 0.02) compared with patients with hypogonadotropic hypogonadism with normal ovaries. After ovarian stimulation, a higher mean serum E2 concentration (P less than 0.001), endometrial thickness (P less than 0.001), and increased number of leading follicles (P less than 0.0001) were found in hypogonadotropic patients with US-diagnosed PCO, compared with hypogonadotropic patients with US findings of normal ovaries. Patients with PCOS had a higher serum E2 concentration (P less than 0.008), although they were treated for fewer days (P less than 0.0001) and with fewer ampules of gonadotropin (P less than 0.001) compared with patients with hypogonadotropic hypogonadism with US-diagnosed PCO. CONCLUSIONS: We have characterized a group of hypogonadotropic patients with US findings of PCO, in which the ovarian response to ovulation induction was similar to patients with PCOS. The results have practical and theoretical implications for the etiology and treatment of patients with PCO.

Adult↗

PubMed1993

Long-term naltrexone treatment normalizes the pituitary response to gonadotropin-releasing hormone in polycystic ovarian syndrome.

OBJECTIVE: To investigate the influence of opioid system on the exaggerated LH response to GnRH test in the polycystic ovarian syndrome (PCOS). DESIGN: Pituitary stimulation (GnRH 100 micrograms) in a group of PCOS patients under basal condition and after 4 weeks of treatment with naltrexone. RESULTS: In the PCOS group, the naltrexone treatment determines a significant reduction of the LH response (calculated as the area under curve) to GnRH test, with a similar significant decrease of the LH:FSH. CONCLUSION: Naltrexone normalizes in the PCOS group the pituitary response to GnRH test, abolishing every statistical differences with the control group.

Adolescent↗

PubMed1993

The relationship between follicle-stimulating hormone dose and level and its relevance for ovulation induction with adjuvant gonadotropin-releasing hormone-agonist treatment.

OBJECTIVE: To investigate the effect of a GnRH agonist (GnRH-a) on the FSH threshold level and the relationship between the FSH dose and the FSH level of patients suffering from polycystic ovarian syndrome (PCOS). DESIGN: The stimulation with low-dose FSH in PCOS (group 1) was compared with the subsequently performed stimulation with low-dose FSH combined with GnRH-a in another group of patients suffering from the same syndrome (group 2). SETTING: Specialist Reproductive Endocrine Unit. PATIENTS: Suffering from clomiphene citrate-resistant PCOS. MAIN OUTCOME MEASURES: The FSH threshold level for ongoing follicular growth and the relationship between dose and level of FSH. RESULTS: In 15 patients in group 1 and in 13 patients in group 2, respectively, 39 and 32 stimulation cycles were performed. Below and above threshold values of FSH of group 1 and 2 did not differ significantly. For the equation stable level of FSH (Y mIU/mL) = A X infusion rate of FSH (X IU/24 h) + basal level of FSH (B mIU/mL), the median A of group 1 was 0.027 and A of group 2 was 0.055 (significant difference). CONCLUSIONS: In PCOS, a change of the FSH threshold level for ongoing follicular growth induced by the GnRH-a could neither be proven nor ruled out. The use of a GnRH-a resulted in larger FSH level increases per IU/24 h of FSH administered and might therefore interfere with the effect of low-dose FSH treatment.

Adjuvants, Pharmaceutic↗

PubMed1994

Low dose ketoconazole attenuates serum androgen levels in patients with polycystic ovary syndrome and inhibits ovarian steroidogenesis in vitro.

OBJECTIVE: To investigate the effects of a low-dose ketoconazole on ovarian steroidogenesis and on serum androgen levels in polycystic ovary syndrome (PCOS). DESIGN: In vitro, human granulosa-luteal cells were incubated with ketoconazole and radiolabeled steroid substrates, to follow their metabolic fate by thin-layer chromatography analysis. In vivo, normally cycling women (n = 7) in their luteal phase were administered one tablet of 200 mg ketoconazole at 8 A.M. Serum steroid levels, sampled basally and at 12 P.M., 4 P.M., and 8 A.M. the next morning, were compared with untreated control group (n = 7) values. Polycystic ovary syndrome women (n = 11) were similarly administered ketoconazole 6 to 10 days after occurrence of spontaneous menses. Adrenal origin of hyperandrogenemia was excluded by stimulation with ACTH and a normal basal DHEAS. The steroid diurnal variation was determined in the same patients a day before treatment. RESULTS: In vitro, ketoconazole selectively inhibited the key steroidogenic cytochromes, namely P450scc, P45017 alpha, and P450arom (IC50 = 0.5 to 1.0 microgram/mL). In vivo, in the luteal phase, ketoconazole transiently decreased serum values (mean +/- SE) of E2 (19.2% +/- 2.1%) and P (38.3% +/- 8.5%) within 4 to 8 hours. The same low-dose ketoconazole, administered to PCOS women, decreased serum values of androstenedione (17.6% +/- 4.7%), T (24.6% +/- 7.6%), and free T (30.7% +/- 7.7%). In contrast, 17 alpha-hydroxyprogesterone increased concomitantly (78.5% +/- 10.8%), suggesting a greater suppressibility of the P45017 alpha lyase activity. The E2 levels in PCOS patients were slightly elevated (29.1% +/- 5.6%), resulting in a 1.7- to 2.3-fold increase of the E2:T ratio. CONCLUSIONS: These findings suggest that a low-dose ketoconazole may facilitate a decreased intraovarian T:E2 ratio, which may prove favorable for follicular maturation in PCOS.

17-Hydroxysteroid Dehydrogenases↗

PubMed1994

Increased insulin secretion in patients with multifollicular and polycystic ovaries and its impact on ovulation induction.

OBJECTIVE: To assess the oral glucose tolerance test (OGTT)-stimulated insulin secretion and its relation to pulsatile GnRH ovulation induction outcome in patients with multifollicular or polycystic ovaries (PCOs). DESIGN: Prospective study. SETTING: Reproductive Endocrinology Center, University of Bologna, Bologna, Italy. PATIENTS: Eight normal and 29 anovulatory women (8 with multifollicular ovaries and 21 with PCOs). INTERVENTION: A standard OGTT was performed in all subjects. In all anovulatory patients, ovulation was induced with pulsatile GnRH (5 micrograms i.v. every 60 minutes). In multifollicular ovary patients, pulsatile GnRH was administered alone, whereas in PCOs it was preceded by GnRH agonist (GnRH-a) suppression. MAIN OUTCOME MEASURES: Glucose, insulin, and C-peptide response to the OGTT, expressed as area under the curve (AUC). Ovulatory rates in response to pulsatile GnRH. RESULTS: Insulin and C-peptide AUC were greater than controls in both multifollicular ovary and PCO patients. Insulin AUC was positively correlated to ovarian volume. Ovulation was achieved in 88% and 57% of multifollicular ovary and PCO patients, respectively. Body mass index and glucose AUC but not insulin and C-peptide AUC were significantly greater in the anovulatory PCO. CONCLUSIONS: [1] Insulin AUC was increased in both multifollicular ovary and PCO patients; [2] derangements of insulin secretion may be present in a greater variety of anovulatory patients than previously thought; [3] insulin levels during the OGTT did not predict a response to pulsatile GnRH in PCOs, suggesting complex insulin interactions at the ovarian level; [4] given the in vitro stimulatory properties of insulin on granulosa cells synergistic with FSH, we propose that excessive insulin levels may contribute to the ovarian enlargement often found in multifollicular ovary and PCO patients.

Adult↗

PubMed1995

Ovarian influence on adrenal androgen secretion in polycystic ovary syndrome.

OBJECTIVE: To determine whether the ovary influences adrenal androgen secretion in polycystic ovary syndrome (PCOS). DESIGN: The adrenal androgen secretion was evaluated before and during ovarian suppression with a long-acting GnRH agonist. SETTING: Department of Obstetrics and Gynecology, Pisa, Italy. PARTICIPANTS: Women with PCOS and high (10 subjects) and normal (12 subjects) DHEAS levels and 6 normal women. INTERVENTIONS: After 1 mg dexamethasone, an ACTH-(1-24) stimulation test was performed in the early follicular phase of the menstrual cycle. The test was repeated after two injections of a long-acting GnRH analogue (GnRH-a). MAIN OUTCOME MEASURES: Basal plasma levels of gonadotropins, E2, T, androstenedione (A), 17 alpha-hydroxyprogesterone (17-OHP), DHEAS, and cortisol (F) were evaluated before the evening administration of dexamethasone. Serum A, T, 17-OHP, DHEAS, and F were measured 9 hours after dexamethasone and in samples collected 60 and 120 minutes after ACTH IV injection. RESULTS: In the high DHEAS group the maximum increases in T, A, 17-OHP, and DHEAS in response to ACTH were significantly higher than in normal DHEAS PCOS women and in normal women. The GnRH-a modified the A and T responses to ACTH in the high DHEAS group. CONCLUSIONS: Ovarian steroids, or other extra-ovarian factors, seem to be responsible for the increased A and T responses to the corticotropin stimulation demonstrated in some PCOS women.

Adolescent↗

PubMed1995

Prorenin is elevated in polycystic ovary syndrome and may reflect hyperandrogenism.

OBJECTIVE: To examine the null hypothesis that women with polycystic ovary syndrome (PCOS) produce similar levels of prorenin and other components of the ovarian-derived prorenin to angiotensin cascade (ODPAC) at baseline and after stimulation with clomiphene citrate (CC) or hMG when compared with normal age- and weight-matched ovulatory controls. DESIGN: Prospective controlled clinical trial. SETTING: Infertility clinic in a university-based county hospital and a hospital-based private infertility practice. PATIENTS: Twenty-eight infertile women aged 18 to 35 years. Thirteen patients were diagnosed with PCOS. Fifteen normal ovulatory patients who were matched for age and weight served as controls. INTERVENTIONS: Twenty patients were stimulated with CC and eight were stimulated with hMG. MAIN OUTCOME MEASURES: Serum E2, P, T, androstenedione (A), DHEAS, LH, FSH, and plasma prorenin, active renin, and angiotensin II (Ang II) were measured at baseline and during the preovulatory and midluteal phases of the stimulation cycles. RESULTS: Baseline plasma prorenin in PCOS was higher than that of follicular phase controls. Plasma prorenin correlated significantly with peripheral androgen levels. Prorenin, active renin, and Ang II increased in response to gonadotropins with the largest increases occurring in control patients receiving CC. An association was seen between ovulation with CC and lower baseline levels of active renin. CONCLUSIONS: The null hypothesis was rejected. Infertile women with PCOS have higher baseline prorenin levels when compared with age- and weight-matched ovulatory controls. There is a significant correlation between prorenin and the peripheral levels of androgens produced during ovarian stimulation. Baseline active renin levels may be predictive of ovulation with CC.

Adolescent↗