Effect of Metformin on Anovulation and Infertility 2211 Metformin Monotherapy in PCOS

Numerous clinical trials have evaluated the effect of metformin on ovulation in women with PCOS. Nester et al. reported the first randomized, placebo-controlled trial evaluating the use of metformin to reestablish ovulation (11). Sixty-one obese women with PCOS were randomized to metformin 500 mg three times daily or placebo for 35 days. If spontaneous ovulation did not occur, they were entered into the second phase of the study and were given clomiphene 50 mg daily for 5 days while continuing...

Perimenopausal Stage

Estradiol and testosterone parameters during the menopausal transition. The concentrations of estradiol and testosterone, their blood production rates, and their metabolic clearance rates are shown for women at various indicated phases of perimenopause. FSH, follicle-stimulating hormone. (Data from ref. 32.) Burger and associates (35) also conducted longitudinal studies of women through the menopausal transition. As found by others, they noted little, if any, change in total...

Background

Infertility and Anovulation PCOS is the most common cause of anovulatory infertility and may account for more than 75 of cases of anovulatory infertility (3). However, not all women with PCOS are completely amenorrheic. The majority of women with PCOS are oligomenorrheic and experience varying intervals of vaginal bleeding. Abnormal ovulatory function associated with PCOS is distinguished by dysfunctional folliculogenesis and abnormal steroidogenesis. Follicular development within the...

Ppp1r3

Plasma cell membrane glycoprotein-1 (PC-1) A promoter VNTR was linked and associated with PCOS and or insulin sensitivity in women with polycystic ovaries in some studies but not others. Analysis of multiple data sets showed no association of the VNTR with PCOS or testosterone levels. An SNP in the tyrosine kinase domain was associated with PCOS, particularly in lean women. Other studies of the insulin receptor in women with PCOS have identified only common, silent polymorphisms. Two...

Background 21 Cosmetic Procedures

Cosmetic procedures may be very helpful in controlling mild-to-moderate degrees of unwanted hair and are virtually always required as an adjunct in women being treated medically to remove existing terminal hair. Reduction in the frequency with which women use cosmetic procedures is also reliable evidence of drug efficacy. In general, these procedures are time-consuming and may be expensive. Complications include pain, discomfort, dyspigmentation, and scarring. Several different techniques may...

Abnormal Estrogen Production

In normally cycling women the predominant site of estrogen production is the granulosa cells of the ovarian follicle. In ovulatory cycles in PCOS, the dominant follicle secretes estradiol in sufficient quantities to trigger the midcycle surge of LH, but in the anovulatory cycles typical of PCOS, follicle development is arrested at the small antral stage when selection of a dominant follicle would normally occur and the aromatase enzyme would be expressed (30). Consequently, the granulosa cells...

Flutamide

Flutamide is a nonsteroidal drug, considered a pure antiandrogen in that it seems to act only at the androgen receptor as a competitive antagonist (20). Some data suggest that flutamide might also reduce synthesis of androgens and or increase their metabolism to inactive molecules, lowering androgen serum levels. This drug is licensed for the treatment of advanced prostatic carcinoma and was successfully evaluated in hyperandrogenic women (21). Flutamide has been administered to hirsute women...

Ovarian Hyperstimulation Syndrome

OHSS is a potentially serious iatrogenic complication of ovarian stimulation with gonadotropins. A controlled study comparing patients with and without polycystic ovaries undergoing IVF showed that 10.5 of the polycystic ovary patients developed moderate severe OHSS compared with none of the controls (13). OHSS is characterized by increased vascular permeability and transudation of protein-rich fluid from the vascular space into the peritoneal cavity. The incidence of severe OHSS ranges between...

Summary

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of functional androgen excess, although its definition remains fluid and controversial. PCOS is characterized by clinical and or biochemical hyperandrogenism and is frequently accompanied by ovulatory dysfunction and polycystic ovaries. PCOS is a diagnosis of exclusion, with other androgen excess and related disorders to be excluded. Two principal definitions are in use today one arising from an expert conference sponsored by the...

Info

AThe measurements were carried out with four different direct testosterone immunoassay kits that included radioactive (RIA) or chemiluminescent (CIA) markers. Comparisons were made to testosterone values determined by conventional RIA. *p < 0.05 (failed test for validity). aThe measurements were carried out with four different direct testosterone immunoassay kits that included radioactive (RIA) or chemiluminescent (CIA) markers. Comparisons were made to testosterone values determined by...

Gonadotropin Ovulation Induction

Exogenous gonadotropins have traditionally been used in PCOS patients who are resistant to ovulation induction with clomiphene and more recently those not responding to the addition of metformin or laparoscopic ovarian drilling. Gonadotropin preparations derived from hMG, a mixture that contains FSH, LH, and large quantities of urinary proteins, have been in use since the early 1960s (97). Other gonadotropin preparations in use today include purified urinary FSH (uFSH) and recombinant FSH...

Medical History and Physical Examination in Patients With Possible Androgen Excess

We outline here the basics of the medical history and physical exam in the patient suspected of suffering from androgen excess. The timing and pace of pubertal development and its relation to complaints of unwanted hair growth, hair loss, acne, and or obesity should be established. The onset and progression of these complaints should also be established. Drug or medication use and exposure or use of skin irritants should be elicited. A detailed menstrual history should be obtained, with an...

Tenascin X Deficiency Pcos

NCAH resulting from 3P-HSD deficiency has been purportedly diagnosed in 1-15 of children with premature pubarche (3,4) and a variable frequency of females with hirsutism and menstrual disorders with pubertal or postpubertal onset (5-7). In these early studies, patients were presumed to suffer from 3 P-HSD-deficient NCAH if they demonstrated a pregnenolone (PREG), 17-hydroxy-pregnenolone (17-HPREG), dehydroepiandrosterone (DHEA), and or androstenediol (ADIOL) peak value, or a PREG P4, 17-HPREG...

Ovarian Stimulation for IVF in Polycystic OvaryPCOS

Ovarian stimulation with gonadotropins for IVF in polycystic ovaries and or PCOS is a particular problem and is indeed a challenge for the physician and patient. The long GnRH agonist-suppression protocol accompanied by pretreatment with combined oral contraceptive pills has been widely accepted as the most effective stimulation protocol for polycystic ovary PCOS patients (Fig. 2). Pituitary suppression takes longer for polycystic ovary PCOS patients (22). Although the optimal time to commence...

Glucocorticoids for Ovulation Induction

The role of adrenal hyperandrogenism in producing oligo-ovulation is unclear, because both dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEAS) are relatively weak androgens. Nevertheless, DHEAS circulates in a concentration 10,000 times that of testosterone, and thus may result in significant androgenicity. Furthermore, circulating DHEAS has been found to be the precursor for almost 50 of testosterone within follicular fluid in women being treated with menotropins (48). Thus, it...

Seborrhea andor Acne

The prevalence of androgen excess among acneic-only patients (excluding patients with hirsut-ism) is less than among hirsute women. In small studies, between 20 and 40 of patients with treatment-resistant acne and without menstrual disturbance, alopecia, or hirsutism are reported to have androgen excess, principally PCOS (30-33). Alternatively, data regarding the predictive ability of seborrhea for androgen excess is lacking. Large populational studies of acneic or hyperseborrheic patients,...

Estimating the Economic Burden of PCOS

We calculated the health care-related economic burden in PCOS based on the above prevalences of disease (64). We restricted the calculation to the United States only, although we recognize that PCOS is an international disorder. However, we should note that our estimation is highly conservative because we did not include a number of costs for which we did not have accurate and present-day prevalence and monetary estimates (Table 1). We did include the costs of the initial evaluation, detailed...

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder associated with type 2 diabetes mellitus, hypertension, dyslipidemia, and insulin resistance (IR) (1). The metabolic features of PCOS have led to widespread concern about concurrent increased cardiovascular risk (CVR). In fact, several studies have demonstrated various cardiovascular and lipid abnormalities in PCOS women. However, to date there is no definitive evidence of increased cardiovascular mortality in PCOS (2)....

IVF in PCOS

Ivf Protocols For Pcos

PCOS is the most common cause of anovulatory infertility. As described in Chapters 35 and 37, the treatment of anovulation comprises lifestyle modification through diet, exercise, and weight loss, insulin sensitizers, oral ovulation induction agents, surgical treatments, and gonadotropins. Patients who have not conceived with other treatment approaches or couples who have additional infertility factors may require IVF. In vitro fertilization treatment outcomes for PCO PCOS patients may even be...

Choice of Insulin Sensitizing Agent in PCOS

Currently, the commercially available insulin-sensitizing agents include metformin and the thiazolidinediones (rosiglitazone and pioglitazone). Most of the clinical studies in women with PCOS have been conducted with metformin. In addition, for several decades metformin has been used worldwide to treat diabetes, and thus its side effect profile has been well described. Adverse effects of metformin include gastrointestinal distress, such as diarrhea and nausea. More serious toxicity includes a...

Polycystic Ovarian Morphology

Polycystic Morphology Left Ovary

Studies, including the one in which we compared 214 patients with PCOS to 112 women with normal ovaries (14). By ROC analysis, a follicle number per ovary (FNPO) of 12 or more follicles of 2-9 mm diameter yielded the best compromise between sensitivity (75 ) and specificity (99 ) for the diagnosis of polycystic ovaries (Table 3). It is not possible to compare these data to the recent modification of their criteria proposed by Adams et al. (9), that is, eight or more cysts 2-8 mm in diameter in...

Metformin Weight Loss and PCOS

The initial use of metformin in the treatment of PCOS has now been widely accepted to be a valuable and inexpensive therapeutic modality. Recent systematic reviews have indicated that metformin is highly effective in inducing ovulation and increasing pregnancy rates (8,9). The numbers needed to treat for ovulation are around four patients, and there is an improvement in serum insulin levels and a reduction in free testosterone in response to metformin. The drug appears to be safe in early...

Nadph

Electron transfer by mitochondrial (type I) P450 enzymes. Nicotinamide adenine dinucleotide phosphate (NADPH) donates a pair of electrons to ferredoxin reductase, which is bound to the inner mitochondrial membrane. The flavin adenine dinucleotide (FAD) moiety of ferredoxin reductase passes the electrons to the iron sulfur center of ferredoxin, depicted by a ball-and-stick diagram. Ferredoxin then dissociates from ferre-doxin reductase, diffuses through the mitochondrial matrix, and...

Cah

0Refers to the severity of the defective enzymatic activity of P45021 determined by the mutation. 'The variations in phenotype with Intron 2 mutations are thought to be caused by the variable region around nucleotide 656, which affects the splicing of the intron, although the exact mechanism has yet to be elucidated. (Adapted from refs. 22-31.) 0Refers to the severity of the defective enzymatic activity of P45021 determined by the mutation. 'The variations in phenotype with Intron 2 mutations...

Effect of Thiazolidinediones on Anovulation and Infertility 2221 Effects of Thiazolidinedione Monotherapy

As described earlier, the largest long-term study evaluating the use of an insulin-sensitizing agent in PCOS has been conducted with troglitazone. In this study, troglitazone (150, 300, or 600 mg daily) was compared to placebo in 305 women with PCOS for 44 weeks (10). Women receiving troglitazone daily at the 300- and 600-mg doses had significantly higher ovulation rates than those receiving placebo. This increase in ovulation rate was dose dependent, suggesting that improvement in insulin...