Background

Hyperandrogenism Women

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic anovulation and hyperandrogenism. The prevalence among women of reproductive age is at least 6 (10). Its pathophysiology, most likely a combination of genetic disposition and environmental factors, is not completely understood (11,12). PCOS is one of the leading causes of infertility and is also characterized by hirsutism, cystic acne, seborrhea, hair loss, and obesity (13,14). A significant proportion of...

Chronic Therapy in PCOS with Insulin Sensitizers

Both metformin and the thiazolidinediones have been shown to reduce blood pressure and inflammatory markers. Obese women on metformin also tend to lose weight while on metformin in a dose-dependent manner (63). Although the insulin sensitizers' effects on cardiovascular risk factors are favorable, currently there are no prospective randomized outcome trials examining the use of insulin sensitizers in the prevention of diabetes or cardiovascular events in women with PCOS. 2.3.2.1. Insulin...

References

Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004 89 453-462. 2. DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005 83 1454-1460. 3. Pasquali R, Gambineri A. Role of changes in dietary habits in polycystic ovary syndrome. Reprod Biomed Online 2004 8 431-439. 4. Rajkhowa M, Talbot JA, Jones...

When Should Insulin Sensitizers Be Used for Ovulation Induction

Although current data suggest that metformin increases the frequency of spontaneous ovulation and improves the efficacy of ovulation induction and clinical pregnancy with clomiphene, large-scale studies with metformin have not been completed. Hence, the optimal therapy or combination of therapies to achieve pregnancy most efficiently is currently unknown. If pregnancy is desired as soon as possible, currently clomiphene is still the historical standard of care until larger-scale studies have...

Insulin Sensitizers and Pregnancy Outcomes

Although ovulatory dysfunction is an important etiological feature of the infertility of PCOS, ovulation is only one aspect of fertility. In addition to ovulatory problems, women with PCOS suffer a high rate of early pregnancy loss (EPL) during the first trimester (30-50 in PCOS vs 10-15 in normal women) (38-42). It is possible that insulin resistance may contribute to EPL by adversely affecting the endometrial environment and or endometrial function. The effect of metformin on endometrial...

Info

12-hour composite LH (mlU mL) No insulin LH pulse frequency (no. 12 hours) No insulin LH pulse amplitude (mlU mL) No insulin Normal vs PCOS ap < 0.01 bp < 0.006. LH, luteinizing hormone PCOS, polycystic ovary syndrome. (From ref. 21.) Normal vs PCOS ap < 0.01 bp < 0.006. LH, luteinizing hormone PCOS, polycystic ovary syndrome. (From ref. 21.) Fig. 1. Time-course of mean (+SE) serum luteinizing hormone (LH) concentrations after intravenous administration of three successive doses of...

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...

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...

Conclusions

Androgenization of women has captivated humankind for millennia, with early recognition of the relationship between menstrual dysfunction and the development of hirsutism and other virilizing features. Most early patients described appeared to suffer from ovarian or adrenal neoplasms, such that the hyperandrogenic symptoms were generally marked. Not until the early 20th century were lesser degrees of hyperandrogenism recognized as meriting medical evaluation, and only in the past century have...

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...

Dermatological Abnormalities Hirsutism Acne and Androgenic Alopecia

We should note that hirsutism is one of the more common signs of androgen excess, in particular in PCOS (10), which has significant psychosocial and quality-of-life implications (56,57). The prevalence and degree of hirsutism, however, is dependent on the ethnicity of the patients apparently it is less prevalent in women with PCOS of East Asian extraction or Pacific Islanders (58,59) but more prevalent in women of Asian Indian origin (e.g., Bengali, Gujarati, or Dravidian Indian) (60). Overall,...

Fsh

Calculated free androgen index total testosterone SHBG (nmol L) Not required for diagnosis Note PCOS-appearing ovaries may be found in normal adolescents. SHBG, sex hormone-binding globulin DHEAS, dehydroepiandrosterone sulfate OGTT, oral glucose tolerance test TSH, thyroid-stimulating hormone FSH, follicle-stimulating hormone PCOS, polycystic ovary syndrome. The majority of adolescents presenting for evaluation of hyperandrogenism will have PCOS, but there is no single definitive test for...

Introduction

The earliest reports of androgen excess, beginning around 400 bc, focused on the appearance of male-like hair growth and features in women, often accompanied by menstrual cessation. Two other pathologies were then recognized, beginning in the late 17th and early 18th centuries, including adrenal pathologies and sclerocystic ovaries. These seemingly separate and disparate observations only begin to converge in the 20th century into the disorders we recognize today. The burgeoning research...

Summary

Between 20 and 30 of patients with polycystic ovary syndrome (PCOS) demonstrate adrenal androgen (AA) excess, detectable primarily by elevated dehydroepiandrosterone sulfate (DHEAS) levels. Generalized adrenocortical hyperresponsivity to adrenocorticotropic hormone (ACTH) stimulation is also observed and may be the principal mechanism determining AA excess in PCOS. The causes of this abnormality are unclear, but increased peripheral metabolism of cortisol, altered factors regulating...

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...

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...

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...

In Vitro Maturation

Transvaginal Oocyte Recovery

The recovery of immature oocytes (Fig. 4) followed by IVM and IVF is an attractive alternative to conventional IVF treatment in which controlled ovarian stimulation with gonadotropins is used to increase the number of available oocytes and embryos (41). Significant progress has been made in improving implantation and pregnancy rates from in vitro matured oocytes (Fig. 4). The high numbers of antral follicles in patients with polycystic ovaries or PCOS make them prime candidates for IVM...

Preface

The field of androgen excess disorders has advanced substantially since the original publication of this book. The Androgen Excess Society (AES) was founded to bring together investigators in the field. A better understanding of the screening, progression, and molecular genetics of nonclassic adrenal hyperplasia (NCAH) has improved the clinical care and diagnostic accuracy of these patients. New criteria for the diagnosis of the polycystic ovary syndrome (PCOS) were proposed in Rotterdam,...

IVF in 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...

Pcos And Risk For Cardiovascular Disease

At this moment there is no single and universally accepted definition for PCOS. This is probably the pivotal reason why published studies on PCOS cannot be easily reanalyzed in order to provide a conclusive assessment of the CVR or CVD in this group of patients. Nevertheless, several lines of evidence (11-15) indicate alterations in intermediate endpoints for CVR in women with PCOS and provide evidence for an association between CVR factors in PCOS and CVD (Table 1). Most studies Evidence for...

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...

Ovarian Sonography

The nuances of ovarian morphology have been reviewed in Chapter 16. It is important here to note that because polycystic ovarian morphology has become an integral part of the diagnosis of PCOS, patients suspected of having androgen excess should undergo transvaginal sonography when possible. Importantly, the definition of polycystic-appearing ovaries is relatively uniform and specific. It should also be understood that although virginal women and others who do not tolerate a transvaginal...

Effect of Insulin Sensitizers on Hirsutism

Current data on the effect of insulin sensitizers on hirsutism are conflicting. In an open-label study of 39 women with PCOS, metformin 500 mg three times daily significantly decreased Ferriman-Gallwey hirsutism scores at the end of the 12-week study period (32). However, in a more rigorous randomized, placebo-controlled, 44-week trial, metformin at the same dose did not significantly reduce clinical hirsutism scores (17). In another randomized controlled 12-month study, metformin 500 mg three...

Pharmacological Options for Ovulation Induction in PCOS

In women with PCOS who are not obese or overweight, who are obese but unable to lose weight, or who fail to ovulate despite weight loss, ovarian stimulation with pharmacological agents is the next step in the treatment of oligo-ovulatory infertility. Clomiphene citrate is currently the first-line pharmacological therapy for ovulation induction, although metformin appears to also be a promising agent for first-line therapy, at least in some patients. Studies are currently ongoing to address...

Effect of Hyperinsulinemia on Anovulation in PCOS

Numerous studies have demonstrated that hyperinsulinemia contributes to the chronic anovulation of PCOS. In the largest long-term study, 305 women with PCOS were randomized to the insulin sensitizer troglitazone 150, 300, or 600 mg daily or placebo for 44 weeks 10 . Women receiving troglitazone at doses of 300 and 600 mg daily had a significantly higher ovulation rate 0.42 and 0.58 than those receiving placebo 0.32 p lt 0.05 and 0.0001, respectively . This increase in ovulation rate was dose...

Anovulation Is A Characteristic Feature Of Pcos. It Manifests As Menstrual Disturbance 80 Amenorrhoea Oligoamenorrhea

Patient With Hyperandrogenism

The features of PCOS may be elicited when obtaining the medical history or upon the physical examination. The ovarian morphological and the biochemical and metabolic features of the disorder are discussed in Chapters 16 and 17. The evaluation of patients with androgen excess, including PCOS, is discussed in Chapter 33. 2.1. Features Elicitable by Medical History In this section, we will outline important information that the medical history will elicit concerning the features of PCOS, including...

Medical History and Physical Examination in Patients With Possible Androgen Excess

Modified Ferriman Gallwey Score

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...

Wiesner G. Vaz M. Collier G. Y Col. Leptin Is Released From The Human Brain Influence Of Adiposity And Gender. J. Clin.

Polycystic ovary syndrome. N Engl J Med 2005 352 1223-1236. 2. Dunaif A. Insulin resistance and the polycystic ovary syndrome mechanisms and implications for pathogenesis. Endocr Rev 1997 18 774-800. 3. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999 20 535-582. 4. Gambineri A, Pelusi C, Vicennati V, Pagotto, U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Rel Metab Dis 2002...

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 are...