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PubMed2001

Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease.

OBJECTIVES: To determine oxidant and antioxidant status in women with polycystic ovary syndrome (PCOS) and its contribution to the risk of cardiovascular disease. DESIGN AND METHODS: 27 women with PCOS were compared with regard to oxidant and antioxidant status with 18 age- and body mass index (BMI)-matched healthy. Oxidant status was evaluated by determination of erythrocyte malondialdehyde (MDA) concentration, while antioxidant status was evaluated by determination of erythrocyte reduced glutathione (GSH) concentration, and glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Area under curve (AUC) for glucose, AUC for insulin and the insulin sensitivity index (ISI) were calculated from two-hour OGTT. RESULTS: Women with PCOS were found to have higher AUC for glucose (p = 0.01), AUC for insulin (p < 0.001), MDA level (p = 0.009) and SOD activity (p = 0.04), and lower ISI (p < 0.001) and GSH level (p = 0.03) than the controls. In correlation analysis, a significant relationship was found between MDA levels and age (p < 0.01), BMI (p < 0.001), waist-to-hip ratio (p < 0.01), systolic and diastolic blood pressures (both p < 0.05), AUCs for glucose and insulin (both p < 0.05), ISI (r = -0.42, p < 0.05) and triglyceride (p < 0.01). CONCLUSIONS: An increase in oxidant status was found in women with PCOS, and this increase was related to central obesity, age, blood pressure, serum glucose, insulin and triglyceride levels and insulin resistance. In contrast, antioxidant status was observed to be insufficient. These findings suggest that increased oxidative stress may contribute to the increased risk of cardiovascular disease in women with PCOS.

Adult↗

PubMed2000

Association of AccI polymorphism in the follicle-stimulating hormone beta gene with polycystic ovary syndrome.

OBJECTIVE: To search for FSH beta-subunit gene mutations in patients with polycystic ovary syndrome (PCOS) and determine the association between the mutations and the syndrome. DESIGN: Clinical and molecular studies. SETTING: Clinics and laboratories of the National University Hospital Obstetrics and Gynecology Department in Singapore. PATIENT(S): One hundred thirty-five patients with PCOS and 105 normal control subjects. INTERVENTION(S): Exons two and three were screened for mutations by single-stranded conformational polymorphism and DNA sequencing. MAIN OUTCOME MEASURE(S): Polymerase chain reaction followed by restriction enzyme analysis. RESULT(S): No missense mutation was found in the functional units of the FSHbeta gene in patients with PCOS, but a thymine-cytosine substitution in exon 3 (codon 76, TAT to TAC) was identified. The nucleotide change led to creation of an AccI digestion site. The distribution pattern of AccI polymorphism in the patients was significantly different from that in the control group, and the occurrence of homozygous carriers was significantly higher in patients (12.6%) than in the control group (3.8%). The frequency of polymorphism and prevalence of homozygosity were significantly higher in patients with PCOS with obesity (0.50% and 31.0%, respectively) than in those with menstrual disorders only (0.366% and 8.5%, respectively), which correlated with significantly higher androgen levels in the obese patients. CONCLUSION(S): The AccI polymorphism in FSHbeta gene may be associated with PCOS in some women, especially those with obesity.

Acne Vulgaris↗

PubMed2001

Increased 6-sulfatoxymelatonin excretion in women with polycystic ovary syndrome.

OBJECTIVE: To determine melatonin production in hyperandrogenic women. DESIGN: Controlled prospective study. SETTING: Outpatients in an academic medical center. PATIENT(S): Twenty-two women with polycystic ovary syndrome (PCOS), 20 women with idiopathic hirsutism, and 15 age-matched individuals who had similar body mass indexes as controls. INTERVENTION(S): Fasting blood samples and 24-hour urinary samples were obtained from all participants. MAIN OUTCOME MEASURE(S): All participants provided serum samples for the measurement of LH, FSH, testosterone, E(2), DHEAS, 17 alpha-hydroxyprogesterone (17-OHP), and insulin levels, as well as urinary 6-sulfatoxymelatonin (aMT6s). RESULT(S): Women with PCOS had higher aMT6s, testosterone, LH/FSH ratio, and insulin values than either women with idiopathic hirsutism or control women. Testosterone inversely correlated with aMT6s in PCOS. Regression analysis revealed that only testosterone was an important determinant of aMT6s in PCOS. CONCLUSION(S): Women with PCOS have increased melatonin production.

Adolescent↗

PubMed2002

Effect of the opioid blockade on the feeding-induced growth hormone response to growth hormone-releasing hormone in women with polycystic ovary syndrome.

OBJECTIVE: To investigate the effect of naloxone, an opioid receptor antagonist, on the release of growth hormone (GH) induced by the growth hormone-releasing hormone (GHRH) in normal-weight and obese women with PCOS in relation to feeding. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Seventeen women with PCOS (10 who were normal weight and 7 who were obese) and 14 control women (7 who were normal weight and 7 who were obese). INTERVENTION(S): A GHRH test (50 microg i.v.) and, on a different day, a GHRH test during a naloxone infusion (1.6 mg/h) during fasting. The same tests were repeated after a standard meal. MAIN OUTCOME MEASURE(S): GH response to GHRH (expressed as the area under the curve [AUC]) in different experimental conditions. RESULT(S): All normal-weight women showed a significantly higher AUC-GH compared with obese women in the fasting state. Normal-weight controls had a decrease in GH response to GHRH after feeding, and naloxone did not reverse the decrease. In obese controls, feeding increased the GH response but naloxone induced a decrease in the AUC. In fasting, normal-weight women with PCOS, naloxone significantly decreased the AUC-GH; in these patients, food intake induced an inhibition of GH response to GHRH, reversed by naloxone infusion. In obese PCOS patients, GH levels did not increase significantly after GHRH stimulation, either in the fasting state or after a meal, and naloxone did not affect these responses. CONCLUSION(S): Factors other than obesity and insulin may be involved in disruption of GH secretion in women with PCOS.

Adult↗

PubMed2003

A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome.

OBJECTIVE: To review the effectiveness of metformin in restoring regular menstrual cycles and ovulation and achieving pregnancy in women with polycystic ovary syndrome (PCOS). DESIGN: Systematic review of pertinent studies identified using the bibliographic databases MEDLINE and EMBASE. References of selected articles identified were hand-searched for additional relevant citations. PATIENT(S): Women with PCOS undergoing treatment with metformin alone, metformin combined with other methods of ovulation induction such as clomiphene citrate (CC) or gonadotropin injections, or metformin combined with in vitro fertilization (IVF). RESULT(S): Thirty published studies were included in the overall review. Studies consisted of 12 randomized controlled trials, two cohort studies, and 16 uncontrolled descriptive studies. Due to a strong variability in the use of metformin according to study population, exposure, and outcome of interest, it was not possible to combine the data of the 12 randomized controlled trials to perform a meta-analysis. Limited data on predominately obese PCOS patients demonstrate that metformin alone improves both restoration of regular menses and spontaneous ovulation, but there are no data supporting an improvement in pregnancy rate. The addition of metformin to CC results in an improved ovulation and pregnancy rate in both unselected and CC-resistant PCOS women. There are insufficient data to make any conclusions on the effect of metformin on FSH ovulation induction or IVF. CONCLUSION(S): The effectiveness and role of metformin in the treatment of PCOS anovulatory infertility in clinical practice is difficult to assess from currently available research. Further well-designed prospective, perhaps multicenter, randomized controlled trials with the primary end point of pregnancy or live-birth rate are required.

Clomiphene↗

PubMed2003

Decreased expression of tissue inhibitor of matrix metalloproteinases in follicular fluid from women with polycystic ovaries compared with normally ovulating patients undergoing in vitro fertilization.

OBJECTIVE: To compare activity of matrix metalloproteinases (MMP) and expression of their tissue-specific inhibitor (TIMP) in the follicular fluid of normally ovulating women and women with the polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: IVF unit and endocrine research unit. PATIENT(S): Fourteen patients undergoing IVF treatment (seven with normal ovulation and seven with PCOS). MAIN OUTCOME MEASURE(S): Activity of MMP-2 and MMP-9 and expression of MMP-1, TIMP-1, and TIMP-2 was measured in follicular fluid of the leading follicles by using gel zymography and immunoblot analysis. RESULT(S): The activity of MMP-2 and MMP-9 and expression of MMP-1 was similar in follicular fluid of normally ovulating patients and patients with PCOS. Significantly lower expression of TIMP-1 was found in follicular fluid of patients with PCOS women compared with normally ovulating patients. CONCLUSION(S): Because MMPs and TIMPs play a role in the physical and chemical structure of the follicular compartment, the decreased expression of TIMP in patients with PCOS may be part of a compensatory process to overcome the physical properties of the thick ovarian capsule.

Adult↗

PubMed2003

Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease.

OBJECTIVE: To determine oxidative stress by the level of protein carbonyls and total antioxidant status (TAOS), and whether oxidative stress is associated with increased risk of cardiovascular disease in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Thirty women with PCOS and 31 healthy control women. INTERVENTION(S): Biometric measures and blood samples collection. MAIN OUTCOME MEASURE(S): C-reactive protein (CRP), lipid fractions, glucose, protein carbonyls, insulin, and other hormone (gonadotropins, androgens) levels and TAOS were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). RESULT(S): The women with PCOS had significantly higher serum fasting insulin, CRP, protein carbonyl levels, HOMA-R, LH levels, and LH/FSH ratios than healthy women. However, TAOS was significantly lower in women with PCOS. TAOS was negatively correlated with fasting insulin, HOMA-R, CRP, and protein carbonyls. Fasting insulin was positively correlated with protein carbonyls. High density lipoprotein (HDL) was inversely associated with fasting insulin, HOMA-R, and protein carbonyls. CONCLUSION(S): Increased oxidative stress and decreased antioxidant capacity may contribute to the increased risk of cardiovascular disease in women with PCOS, in addition to known risk factors such as insulin resistance, hypertension, central obesity, and dyslipidemia.

Adolescent↗

PubMed1992

Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis.

OBJECTIVES: To provide an up-to-date review of studies that have examined the physiological effects of insulin and insulin-like growth factor I (IGF-I) on ovarian growth, maturation, and steroid synthesis, their physiological role in puberty, and their pathophysiological role in polycystic ovarian syndrome (PCOS). To deduce from these data a hypothesis, explaining the pathogenetic connections between puberty and PCOS. DATA IDENTIFICATION: The most relevant studies related to this topic have been identified through a computerized bibliographic search (MEDLINE) and through manual scanning of what has been published during recent years in the most important journals in the field of reproductive endocrinology. RESULTS: Insulin and IGF-I stimulate ovarian growth and potentiate the actions of gonadotropins on ovarian steroid synthesis. Insulin also augments the bioactive concentrations of IGF-I and androgens through regulation of the synthesis of their respective binding proteins insulin-like growth factor-1 binding protein (IGFBP-1) and sex hormone-binding globulin (SHBG) in the liver. Insulin and IGF-I might also be able to increase the adrenal sensitivity to adrenocorticotropic hormone (ACTH). Insulin resistance with compensating hyperinsulinism is a common feature of PCOS. It is also a normal phenomenon during puberty. Polycystic ovarian syndrome often develops during puberty. Ultrasonographic investigations suggest that it is much more common during adolescence than generally assumed. Actually, there is a striking resemblance between the endocrine characteristics of puberty and some forms of PCOS. Both conditions are characterized by insulin resistance, hyperpulsatile gonadotropin secretion, hyperactive ovarian and adrenal androgen synthesis, and decreased levels of IGFBP-1 and SHBG. CONCLUSION: We propose the progressively increasing insulin levels and IGF-I activity during puberty as inducing factors in the development of PCOS in susceptible subjects.

Female↗

PubMed1993

Diminished growth hormone responses to L-dopa in polycystic ovarian disease.

OBJECTIVE: To investigate the GH secretion capacity in polycystic ovarian syndrome (PCOS). DESIGN: Prospective. SETTING: Reproductive endocrinology unit. PATIENTS: Nineteen women with clinical and endocrinologic signs of PCOS were compared with 10 healthy weight-matched volunteers with normal menstrual rhythm and no history of endocrine or reproductive abnormality. INTERVENTIONS: Standard GH reserve estimates were affected in all subjects using oral L-Dopa. The test was carried out after an overnight fast on cycle days 5 to 8 in menstruating subjects; the test was done randomly in patients with amenorrhea. RESULTS: Both PCOS and control groups responded to L-Dopa over a 3-hour period with significant elevations in GH concentrations. The control group showed significantly higher values than the PCOS group at 90, 120, and 180 minutes. CONCLUSION: The findings indicate that PCOS patients demonstrate a relative deficiency in GH reserve.

Adolescent↗

PubMed1994

Transvaginal ultrasonic assessment of the response to clomiphene citrate in polycystic ovarian syndrome.

OBJECTIVE: To study the relationship between some ovarian morphological findings based on transvaginal ultrasound (US) and the clomiphene citrate (CC) responsiveness in patients with polycystic ovarian syndrome (PCOS). DESIGN: A comparative study of ovarian US features between the CC responders and the CC nonresponders. SETTING: Infertility and Endocrine Clinic, Department of Obstetrics Gynecology, Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Forty-seven infertile patients with PCOS and 30 healthy volunteers. INTERVENTIONS: A dose of 50 to 200 mg/d CC was given for ovulation induction in patients with PCOS. MAIN OUTCOME MEASURES: Ovarian volume and number of follicles; serum LH, FSH, T, delta 4 androstenedione, and DHEAS. RESULTS: The mean ovarian volume (11.9 mL) and the number of small follicles (13.0) were significantly larger in the CC nonresponders compared with those of the CC responders (7.9 mL and 7.0, respectively). Only 47% of the CC responders and 79% of the CC nonresponders had bilaterally enlarged ovaries (> 6.2 mL). Considerable overlap existed between the different groups. However, 96% of the CC nonresponders had a significantly increased number of follicles (> or = 10 follicles) in each ovary compared with that (16%) of the CC responders. Furthermore, with the combination of these parameters, none of the CC nonresponders had bilaterally normal ovaries, and 96% of patients with PCOS with bilaterally abnormal ovaries were CC nonresponsive. CONCLUSIONS: Small multiple follicles (> or = 10) and enlarged ovarian volume (> 6.2 mL) were the most prominent transvaginal US features of ovaries in patients with PCOS with CC nonresponsiveness. These US features could be clinically useful for distinguishing clearly a CC nonresponder from a CC responder.

Adolescent↗

PubMed1994

In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients.

OBJECTIVE: To determine the maturational and developmental competence of immature oocytes recovered in situ from anovulatory and ovulatory patients with polycystic ovaries (PCO). DESIGN: A newly designed method for recovery of immature oocytes from 2 to 10 mm follicles by transvaginal ultrasound or laparoscopy was used to compare the recovery and maturation of oocytes from 9 anovulatory polycystic ovarian syndrome (PCOS) patients and 10 ovulatory patients without polycystic ovaries (PCO) (experiment 1). In a second study (experiment 2), we compared the maturation, fertilization, and development of oocytes recovered from another 10 anovulatory PCOS and 13 ovulatory PCO patients. Two types of culture methods and time intervals for maturation were also examined. RESULTS: In experiment 1, a significantly higher number of immature oocytes were recovered from PCOS patients (15.3) compared with non-PCO patients (2.8). Sixty-five percent of oocytes cultured in medium with gonadotropins, estrogen, and fetal calf serum matured to metaphase II by 43 to 47 hours, and 81% were mature at 48 to 54 hours of culture. Thirty-four percent of the inseminated oocytes fertilized and 56% of the cultured pronuclear oocytes cleaved to eight cells or more. In experiment 2, there was no significant difference between anovulatory PCOS and ovulatory PCO patients in the number of oocytes recovered or their maturation, fertilization, and development. There was no difference between oocytes matured in medium or in coculture with mature granulosa cells, with or without added hCG. However, significantly fewer oocytes were immature and more fertilized when oocytes were inseminated after 34.5 to 35.5 hours of maturation than 29.5 to 32.5 hours of maturation. A pregnancy and the birth of a normal baby occurred in one of the anovulatory PCOS patient receiving an abbreviated steroid replacement protocol after ET. CONCLUSION: Immature oocyte recovery could be developed as a new method for the treatment of women with infertility due to PCO because the oocytes of these patients retain their maturational and developmental competence.

Anovulation↗

PubMed1995

Ethnic differences in insulin and glucose response to glucose between white and Indian women with polycystic ovary syndrome.

OBJECTIVE: To examine different patterns of glucose and insulin secretion in women (of both Indian and white ethnic backgrounds) with polycystic ovary syndrome (PCOS). DESIGN: A 75-g oral glucose tolerance test was performed in 11 subjects from each group. SETTING: Reproductive Medicine and Gynecological Clinics from The Queen Elizabeth Hospital, Woodville, South Australia, and King Edward the VIIIth Hospital, Durban, South Africa. PATIENTS: Couples were grouped as follows: Indian nonobese and obese PCOS, Indian nonobese and obese reference subjects, white nonobese and obese PCOS, white nonobese and obese reference subjects. MAIN OUTCOME MEASURE: Insulin and glucose in plasma after oral glucose testing. RESULTS: Indian PCOS and nonobese reference subjects had higher insulin responses than whites. The ethnic difference was less pronounced in obese women. There were no ethnic differences in glucose response. CONCLUSION: This study demonstrates that the ethnic background of subjects with PCOS needs to be considered in studies on the metabolic parameters in this condition.

Adolescent↗

PubMed1995

Corticotropin-releasing hormone induces an exaggerated response of adrenocorticotropic hormone and cortisol in polycystic ovary syndrome.

OBJECTIVE: To evaluate pituitary-adrenal responsive to corticotropin-releasing hormone (CRH) stimulus in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. PATIENTS: Twelve women aged 17 to 32 years, who had been diagnosed as having PCOS, were studied. Fifteen appropriately age- and weight-matched ovulatory patients served as the control. INTERVENTION: In the early follicular phase or after progestin-induced menses, human CRH was injected at 8:00 A.M. and blood samples were collected at 0, 15, 30, 60, and 90 minutes after stimulus. Plasma levels of ACTH and cortisol were measured. RESULTS: Baseline levels of ACTH and cortisol were similar in PCOS and control patients. Both ACTH and cortisol response to CRH were markedly greater in the PCOS population as compared with controls. Moreover, ACTH- and cortisol-stimulated secretion was prolonged for the whole period of the study in hyperandrogenic patients with respect to controls, where baseline levels were attained 60 minutes after the stimulus. CONCLUSIONS: Our results are consistent with the hypothesis that women with PCOS may demonstrate hyperfunction of the hypothalamic-pituitary-adrenal axis, which may be involved in the physiopathologic events leading to the complexity of the syndrome.

Adolescent↗

PubMed1996

Serum from women with polycystic ovary syndrome inhibits fertilization and embryonic development in the murine in vitro fertilization model.

OBJECTIVE: To study the effects of serum collected from women with polycystic ovary syndrome (PCOS) on the fertilization and early embryonic development of the murine oocyte. DESIGN: Sera from women with anovulation were used as a supplement in a murine IVF model. SETTING: Tertiary care academic medical center. PATIENTS: Four fertile, four hypothalamic amenorrheic, seven PCOS (three with elevated LH and four with elevated T), and three anovulatory women with normal hormone levels. RESULTS: When compared with serum from fertile women, serum from women with PCOS reduced fertilization rates (60% versus 42%) and subsequent early embryonic development rates (87% versus 31%). Serum from women with PCOS and elevated T levels had the lowest fertilization rates (22%). Polycystic ovary syndrome serum with elevated T or LH levels significantly decreased early embryonic development rates in comparison to fertile women (22%, 41% versus 87%). CONCLUSIONS: Serum from women with PCOS inhibited fertilization and blastocyst development. Because both T and LH caused inhibited blastocyst development, these data have implications regarding low pregnancy rates and live birth rates during ovulation induction in women with anovulation. These data also raise questions regarding the use of serum during IVF.

Amenorrhea↗

PubMed1997

Müllerian-inhibiting substance in follicular fluid and serum: a comparison of patients with tubal factor infertility, polycystic ovary syndrome, and endometriosis.

OBJECTIVE: To determine Müllerian inhibiting substance (MIS) levels in follicular fluid (FF) and sera of IVF patients. DESIGN: Prospective study. SETTING: Fertility center. PATIENT(S): Sixty-six patients: 20 with tubal factor infertility, 17 with polycystic ovary syndrome (PCOS), and 29 with endometriosis. INTERVENTION(S): All patients underwent ovarian stimulation with hMG and/or FSH, as well as oocyte retrieval for IVF. MAIN OUTCOME MEASURE(S): Follicular fluid and serum MIS levels and oocyte fertilization rates. RESULT(S): Levels of MIS in FF and sera of PCOS patients were significantly higher than those in tubal factor patients: 7.01 +/- 1.52 versus 1.65 +/- 0.23 ng/mL (mean +/- SE) and 2.97 +/- 0.52 versus 0.92 +/- 0.19 ng/mL, respectively. In endometriosis patients, follicular fluid and serum MIS levels were not significantly different from those in tubal factor patients. In PCOS patients, the percentage of immature oocytes retrieved (17.9% +/- 5.0%) was significantly higher compared with tubal factor (1.5% +/- 1.0%) and endometriosis (9.2% +/- 2.3%) patients. The percentage of oocytes fertilize was significantly lower in PCOS patients (30.2% +/- 5.3%) compared with tubal factor (62.2% +/- 5.5%) and endometriosis (37.5% +/- 5.7%) patients. CONCLUSION(S): Women with PCOS had higher serum and follicular fluid MIS levels, a higher percentage of immature oocytes, and lower fertilization rates than women with endometriosis or pelvic adhesions.

Adult↗

PubMed1999

Do hyperandrogenic women with normal menses have polycystic ovary syndrome?

OBJECTIVE: To determine the prevalence of polycystic ovary syndrome (PCOS) among hyperandrogenic women who report normal menses. DESIGN: Prospective observational study. SETTING: Academic practice in reproductive endocrinology. PATIENT(S): Fifty-eight consecutively seen new patients with hyperandrogenism who reported normal menses. INTERVENTION(S): Ovulatory status was assessed with timed serum progesterone measurements. The following tests also were carried out: vaginal ultrasound examination; measurement of the ovarian response of 17-hydroxyprogesterone (17-OHP) after the administration of leuprolide acetate, 1 mg SC; and determination of fasting serum LH, FSH, E2, 17-OHP, insulin, and androgen levels. MAIN OUTCOME MEASURE(S): Determination of ovulatory status, polycystic appearance of ovaries, and increased response of 17-OHP to leuprolide acetate. RESULT(S): Twelve (20.7%) of the hyperandrogenic women were anovulatory and met the usual criteria for the diagnosis of PCOS. The ovulatory patients had lower serum total and unbound testosterone levels. Thirty-one (53.4%) of the ovulatory women had polycystic ovaries on ultrasound examination and/or an increased 17-OHP response to leuprolide acetate, suggesting the diagnosis of PCOS despite the presence of ovulation. Considering both the anovulatory and ovulatory patients, 74% of the hyperandrogenic women studied could have PCOS. CONCLUSION(S): The data suggest that most (74%) hyperandrogenic women who report normal menses have evidence for the diagnosis of PCOS.

17-alpha-Hydroxyprogesterone↗

PubMed1999

Adrenal dynamic responses to physiologic and pharmacologic adrenocorticotropic hormone stimulation before and after ovarian steroid modulation in women with polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that in women with polycystic ovary syndrome (PCOS), adrenal cytochrome P450c 17alpha activity is different after physiologic vs. pharmacologic ACTH stimulation and that ovarian activity promotes adrenal hyperactivity that is different after physiologic vs. pharmacologic ACTH stimulation. DESIGN: Prospective controlled pilot study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENT(S): Six women with PCOS who had adrenal hyperandrogenism were compared with four women with normal ovulation. INTERVENTION(S): Adrenal dynamic blood sampling was performed before and after 6 months of GnRH agonist administration. MAIN OUTCOME MEASURE(S): Comparison of physiologic and pharmacologic ACTH-stimulated levels of progesterone, 17-hydroxyprogesterone, and androgens before and after ovarian steroid modulation. RESULT(S): In women with PCOS, exaggerated responses of androstenedione and 11beta-hydroxyandrostenedione as well as elevated ratios of 17-hydroxyprogesterone to progesterone and of androstenedione to 17-hydroxyprogesterone after physiologic ACTH stimulation did not persist after GnRH-agonist administration. Three of the six women with PCOS had an increased response of androstenedione and a ratio of androstenedione to 17-hydroxyprogesterone that were >2 SD above the mean of those in the women with normal ovulation after pharmacologic ACTH stimulation; this finding persisted after GnRH-agonist administration. CONCLUSION(S): In women with PCOS, increases in adrenal androgen sensitivity after physiologic ACTH stimulation reflected in both arms of cytochrome P450c 17alpha activity may be influenced by ovarian activity. However, 17,20-lyase hyperactivity in a subset after pharmacologic ACTH stimulation may be an intrinsic adrenal disorder.

Adrenocorticotropic Hormone↗

PubMed1999

Octreotide is not useful for clomiphene citrate resistance in patients with polycystic ovary syndrome but may reduce the likelihood of ovarian hyperstimulation syndrome.

OBJECTIVE: To determine whether octreotide is effective for ovulation induction in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate resistance or for reduction of the risk of ovarian hyperstimulation syndrome (OHSS) with gonadotropin therapy. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Private infertility practice. PATIENT(S): Twelve patients with PCOS undergoing therapy for infertility. INTERVENTION(S): The patients were assigned randomly to receive either octreotide or placebo. Those with clomiphene citrate-resistant PCOS received clomiphene citrate, 150 mg. Patients at risk for the development of OHSS received urinary FSH for ovulation induction. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy, the development of OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E2, LH, and FSH. RESULT(S): Octreotide significantly reduced levels of fasting insulin, insulin-like growth factor 1, and LH in both clomiphene citrate- and urinary FSH-stimulated cycles. Levels of insulin-like growth factor binding protein 3 were increased. Two of six clomiphene citrate-stimulated cycles reached ovulation with the use of either octreotide or placebo. In urinary FSH-stimulated cycles, patients who received octreotide had significantly lower E2 levels at the time of hCG administration and fewer mature follicles. No cases of OHSS occurred in either group. One pregnancy occurred in each group. CONCLUSION(S): Octreotide was no more effective than placebo for clomiphene citrate resistance in patients with PCOS, but it did reduce E2 levels and follicle numbers when combined with urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with PCOS.

Adult↗