Polycystic ovarian syndrome and

Metformin works best in patients with significant hyperglycemia and is often considered first-line therapy in the treatment of mild to moderate type II overweight diabetics who demonstrate insulin resistance. The United Kingdom Prospective Diabetes Study demonstrated a marked reduction in cardiovascular comorbidities and diabetic complications in metformin-treated individuals. Metformin has also been used to treat hirsutism in individuals with polycystic ovarian syndrome and may enhance fertility in these women, perhaps by decreasing androgen levels and enhancing insulin sensitivity. 

Metformin is increasingly being used in the polycystic ovarian syndrome and therefore in lactating women. In seven breastfeeding mothers taking a median dose of 1500 mg/day, the mean relative infant dose transferred in the milk was 0.28% (120). Serum metformin concentrations were very low or undetectable in infants and they appeared to be healthy. A specific warning was given for children with impaired renal function (prematurity, renal insufficiency). 

In women with a functional hypothalamic-hypophyseal-ovarian system and adequate endogenous estrogen production, clomiphene is used to induce ovulation in conditions such as polycystic ovarian syndrome and dysfunctional bleeding with anovulatory cycles. 

Polycystic ovarian syndrome and menstrual irregularities were more prevalent in those taking valproate within a population of 71 women with epilepsy who had taken antiepUeptic drugs for a minimum of 2 years [385. There was no correlation between dose and duration of treatment and the probabilities of such complications. 

As noted above, many of the AEDs induce hepatic microsomal enzyme systems and thus reduce the effectiveness of hormonal contraceptives. Women taking AEDs that may reduce the effectiveness of hormonal contraceptives should be encouraged to also use other forms of birth control. Due to induction or inhibition of sex hormone metabolism and changes in binding of hormones to sex hormone binding globulin, some AEDs may reduce fertility. For example, valproate has been associated with a drug-induced polycystic ovarian syndrome. Women who experience difficulties with fertility should seek the advice of health care professionals with expertise in fertility. 

In infertile women choosing in vitro fertilization, naferelin in combination with gonadotrophins can be used for stimulating ovulation. It is also useful in management of uterine leiomyoma, benign prostatic hypertrophy, hirsutism and polycystic ovarian syndrome. 

While a recent review concluded that there is evidence of neuroendocrine perturbations with VPA, it was also noted that well-controlled monotherapy studies are limited. Given the apparent increased incidence of polycystic ovarian syndrome (PCOS) associated with VPA therapy and uncertainty about the mechanism (e g., weight gain, interference with steroid metabolism), further study is warranted and clinicians should carefully monitor female patients on this agent for increased testosterone levels. Other strategies to minimize the risk of this complication include the following ... 

Some helpful evidence comes from related fields. It should be borne in mind, for example, that the question of an increased risk of endometrial hyperplasia and endometrial cancer also arises in patients with estrogen-producing tumors of the ovaries, obesity, and polycystic ovarian syndrome (101) and in patients with breast cancer who are using tamoxifen (102). 

The use of metformin in polycystic ovarian syndrome, which is often accompanied by insulin resistance or other aspects of the metabolic syndrome, has been systematically reviewed (101). Metformin was therapeutically less effective than weight loss. Adverse effects were nausea, vomiting, and gastrointestinal disturbances. 

The number of individuals affected by reproductive disorders is difficult to assess, and few population-based data are available for either men or women. Noticeably absent are data on fecundity and fertility impairments affecting men and only limited information on male-mediated developmental outcomes exists. Population-based data for impaired female fertility are available for select endpoints from the National Surveys of Family Growth (NSFG), which are conducted periodically and most recently in 1995. Data from the NSFG show that 6.2 million women (10.2%) between the ages of 15 and 44 in the United States had impaired fertility in 1995 (Stephen 1996). This number was estimated to increase to 6.3 million women in 2000 (Stephen and Chondra 1998). Other reproductive disorders in females that impact fecundity include endometriosis and polycystic ovarian syndrome (PCOS). The prevalence of endometriosis in women of reproductive age is reported to be 10% (Houston 1984 Olive and Schwartz 1993), and no population-based prevalence data exist for PCOS. 

Veldhuis JD, Pincus SM, Garcia-Rudaz MC, Ropelato MG, Escobar ME, Barontini M. Disruption of the synchronous secretion of leptin, LH, and ovarian androgens in nonobese adolescents with the polycystic ovarian syndrome. J Clin Endocrinol Metab 2001 86 3772-8. 

This clinical presentation combined with the biochemical findings of increased LH and testosterone are typical of the polycystic ovarian syndrome. Ultrasound examination of her ovaries would confirm the diagnosis. 

Magnetic resonance (MR) imaging is suitable for assessing female infertility, as infertility typically results from benign processes in women of reproductive age. The causes of female infertility include ovulatory disorders (i.e., pituitary adenoma and polycystic ovarian syndrome), disorders of the fallopian tubes (i.e., hydrosalpinx and pelvic inflammatory disease), uterine disorders (i.e.,mullerian duct anomaly, aden-omyosis, and leiomyoma), and pelvic endometriosis. 

Follicle growth is usually monitored with US, and the usefulness of MR imaging is not proved. On T2-weighted images, polycystic ovarian syndrome appears as multiple tiny hyperintense peripheral cysts with hypointense central stroma [23,24] (Fig. 16.12). However, MR imaging findings are nonspecific and serve only as supportive evidence of polycystic ovar-... 

Evaluation of association between the CYPlla promoter pentannucleotide (TTTTA)n polymorphism and polycystic ovarian syndrome among Han Chinese women. Neuro Endocrinol Lett 30 56-60... 

Sangeeta S. Metformin and pioglitazone in polycystic ovarian syndrome a comparative study. J Obstet Gynaecol India 2012 62(5) 551-6. Walter B, Schrettenbrunner 1, Vogelhuber M, Grassinger J, Bross K, Wilke J, et al. Pioglitazone, etoricoxib, interferon-a, and metronomic capecitabine for metastatic renal cell carcinoma final results of a prospective phase 11 trial. Med Oncol 2012 29(2) 799-805. 

In polycystic ovarian disease, both of the generally enlarged ovaries contain many small follicular cysts (2-6 mm), but larger cysts may also be present. Polycystic ovarian syndrome (Stein-Leventhal syndrome) is characterized by the association of polycystic ovaries with irregular menses, prolonged uterine bleeding, amenorrhea, anovulation, and often hirsutism and obesity. The clinical manifestation of this syndrome begins at or shortly after puberty. 

Polycystic ovarian syndrome (PCOS) PCOS patients and controls 171 Blood Higher BPA levels in women with PCOS compared to controls Kandaraki et al. (2011)... 

Human studies also have reported associations between BPA exposures and female reproductive abnormalities, including effects on the ovary, uterus, and oocyte quality. Studies of BPA effects on ovarian morphology are limited and have focused on polycystic ovarian syndrome (PCOS). One case control study (71 women with PCOS and 100 women without) reported a positive association between serum BPA levels and PCOS (Kandaraki et al. 2011). In three studies of women undergoing in vitro fertilization (IVF), BPA exposure was associated with a decrease in peak serum estradiol levels prior to oocyte retrieval, which may have negative effects on embryo quality (Ehrlich et al. 2012b Mok-Lin et al. 2010 Bloom et al. 2011a). 

Urine-derived urofollitropin and recombinant FSH appear to be equally effective and well tolerated for induction of ovulation (34). However, it is unclear whether human menopausal gonadotropins have a higher risk of overstimulation and ovarian hyperstimulation syndrome than urofollitropin in women with polycystic ovary syndrome. 

OHSS is characterized by cystic ovarian enlargement, increased capillary permeability, and third space fluid accumulation (that is in an extracellular compartment that is not in equilibrium with either the extracellular or intracellular fluid, for example the bowel lumen, subcutaneous tissues, retroperitoneal space, or peritoneal cavity). Risk factors include a previous history of OHSS, age under 30 years (probably because more follicles are available), and polycystic ovary syndrome. Non-pregnant patients usually recover within 14 days with supportive treatment. The severe form (with ascites or pleural effusion and hemoconcentration) occurs in 1-10% of patients (64,65). In critical cases, hypoxemia, renal insufficiency, thromboembolism, and rarely death can occur (66). 

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