Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intra-uterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.

Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits.

Polycystic ovary syndrome (PCOS) is an endocrine disorder among women of reproductive age characterized by chronic anovulation and polycystic ovary morphology and/or hyperandrogenism. Management of clinical manifestations of PCOS, such as menstrual irregularities and hyperandrogenism symptoms, includes lifestyle changes and combined hormonal contraceptives (CHCs). CHCs contain estrogen that exerts antiandrogenic properties by triggering the hepatic synthesis of sex hormone-binding globulin that reduces the free testosterone levels. Moreover, the progestogen present in CHCs and in progestogen-only contraceptives suppresses luteinizing hormone secretion. In addition, some types of progestogens directly antagonize the effects of androgens on their receptor and also reduce the activity of the 5α reductase enzyme. However, PCOS is related to clinical and metabolic comorbidities that may limit the prescription of CHCs. Clinicians should be aware of risk factors, such as age, smoking, obesity, diabetes, systemic arterial hypertension, dyslipidemia, and a personal or family history, of a venous thromboembolic event or thrombophilia. This article reports a narrative review of the available evidence of the safety of hormonal contraceptives in women with PCOS. Considerations are made for the possible impact of hormonal contraceptives on endocrine, metabolic, and cardiovascular health.

The telomere attrition rate is not accelerated in women born small for gestational age: A birth cohort study.

BACKGROUND: Physiologically, a reduction in telomere length (LTL) occurs with aging, but epigenetic changes may accelerate telomere shortening and also facilitate the onset of oxidative/inflammatory stress and the development of clinical/metabolic comorbidities in life spam. Although individuals born small for gestational age (SGA) may be related to those epigenetic changes, the assessment of LTL in individuals born SGA has yielded conflicting results (only cross-sectional studies) and has not been carried out in longitudinal studies. We performed a birth cohort study to evaluate the rate of telomere erosion in women born SGA in comparison to women born appropriate for gestational age (AGA) assessed at two different time points during the third decade of life. In our research, born SGA or AGA showed no difference in LTL shortening during a period of five years in the third decade of life. Our finding may have implications for understanding the natural history of diseases in lifespan because the same women (under the influence of similar environmental factors) may be accessed in different phases of life. Thus, the analysis of the present cohort population at a more advanced age may reveal a dynamics of telomere shortening different from here and its possible relation with onset of age-related diseases.

Levonorgestrel-Releasing Intrauterine System for Women With Polycystic Ovary Syndrome: Metabolic and Clinical Effects.

Polycystic ovary syndrome (PCOS) is related to clinical and metabolic comorbidities that may limit the prescription of combined hormonal contraceptives, with consequent need to use progestogen-only contraceptives (POCs). Thus, the objective of the present study was to evaluate the clinical and metabolic effects of a POC, the levonorgestrel-releasing intrauterine system (LNG-IUS), in women with PCOS followed up over a period of 6 months compared to baseline and to women without PCOS. Thus, an observational, prospective, controlled study was conducted on 30 women with a diagnosis of PCOS who presented adverse effect secondary to the use of combined oral contraceptives (nausea, headache, mastalgia or vomiting; PCOS group) paired with 30 ovulatory women without PCOS (control group), both groups being free of comorbidities and having chosen the LNG-IUS as contraceptive. Clinical, laboratory, and ultrasonographic variables were evaluated immediately before LNG-IUS insertion and 6 months after the use of this method. Before LNG-IUS insertion, the PCOS group had higher total testosterone levels (P = .04), lower HDL levels (P = .04), and greater ovarian volume (P < .01) than the control group. Six months after LNG-IUS insertion, there was a 2.3% increase in abdominal circumference (P = .04) and a 3.4% increase in fasting glycemia (P = .02). On the other hand, mean ovarian volume was 10% smaller compared to the volume found before LNG-IUS insertion (P = .04), LDL levels were reduced by 5.2% (P = .03), and total cholesterol levels were reduced by 6.7% (P < .01) compared to baseline evaluation in the PCOS group. The remaining variables did not differ significantly during the 6 months of observation. The control group did not show significant changes compared to the period before LNG-IUS insertion. When the groups were compared after the 6-month follow-up, only glycemia showed a statistically significant variation between the groups, with glycemia levels increasing by 3.4% in the PCOS group and decreasing by 2.6% in the control group (P = .008). In conclusion, the use of the LNG-IUS for 6 months was not associated with relevant changes in clinical or metabolic variables of women with no comorbidities regardless of the presence of PCOS.

Oocyte diameter as a predictor of fertilization and embryo quality in assisted reproduction cycles.

OBJECTIVE: To assess the impact of the mean oocyte diameter (MOD) on occurrence of fertilization and embryo quality in assisted reproduction cycles. DESIGN: Prospective observational study. SETTING: Sector of Human Reproduction of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCFMRP-USP). PATIENT(S): Thirty-five women undergoing intracytoplasmic sperm injection (ICSI) at the University Hospital of Ribeirão Preto from May to October 2007. INTERVENTION(S): MOD assessment. MAIN OUTCOME MEASURE(S): Occurrence of fertilization and qualitative embryo classification on 2nd and 3rd day after ICSI. RESULT(S): We divided 160 metaphase II oocytes according to MOD into groups A (MOD below the 25th percentile), B (MOD between 25th and 75th percentile), and C (MOD above the 75th percentile). There was no statistically significant association between MOD and the occurrence of fertilization or the qualitative embryo classification on days 2 and 3. There was no statistically significant difference between groups regarding number of cells or the qualitative embryo classification on days 2 and 3. CONCLUSION(S): The MOD of mature oocytes does not seem to be related to the occurrence of fertilization or to the developmental quality of human embryos on days 2 and 3 after ICSI.