Cardiovascular risk and combined oral contraceptives: clinical decisions in settings of uncertainty.

Although generally safe, combined oral contraceptives (COCs) are associated with risks, including an estimated 2-fold increased relative risk of cardiovascular events. For most women taking COCs for contraception, absolute cardiovascular risks are very low, and the overall risks of COCs are outweighed by the risks of unwanted pregnancy. Nonetheless, risks of COCs may be excessive in some women, and both the American College of Obstetricians (ACOG) and the World Health Organization (WHO) have offered contraindications for COC use. Complicating this issue, COCs are commonly used for reasons other than contraception (eg, polycystic ovary syndrome, which is associated with subfertility and cardiovascular risk factors). Thus, in some clinical scenarios, ACOG and WHO guidelines may offer incomplete guidance regarding whether COC use would be associated with an unacceptable risk-benefit ratio. We propose that cardiovascular risk calculators may be helpful in some patients, as an adjunct to ACOG and WHO guidelines, by allowing physicians to estimate the attributable risk of COC-related cardiovascular events.

Go Girls!-Dance-Based Fitness to Increase Enjoyment of Exercise in Girls at Risk for PCOS.

Weight loss can reduce the hyperandrogenemia associated with polycystic ovary syndrome (PCOS) in peripubertal girls. Yet, adolescent girls have the lowest rates of physical activity and enjoyment of exercise. We created a dance-based support group (Go Girls!) to entice physical activity and improve enjoyment. Girls ages 7-21 over the 85th BMI percentile were recruited and attended once-weekly sessions for 3-6 months. We assessed changes in Physical Activity Enjoyment Scale (PACES), anthropometrics, laboratory data, and amounts of home exercise at 0, 3, and 6 months. Sixteen girls completed either 3 or 6 months. PACES scores were surprisingly high at baseline and remained high. Systolic blood pressure percentile decreased post-intervention. Although no group differences were observed, the majority of individual girls had decreased waist circumference, triglycerides, and metabolic syndrome severity score. Forty percent had decreased free testosterone levels. More girls enjoyed physical education class, got exercise outside of school, and made other lifestyle changes. This dance-based support group was enjoyed by girls and demonstrated health benefits. Continued efforts to engage girls in physical activity are necessary to protect girls from the consequences of obesity, including PCOS and metabolic syndrome. Dance exercise remains a promising tool to encourage physical activity in girls.

Blunted day-night changes in luteinizing hormone pulse frequency in girls with obesity: the potential role of hyperandrogenemia.

CONTEXT: Puberty is marked by sleep-associated changes in LH pulse frequency and amplitude. Early pubertal girls with obesity exhibit blunted day-to-night changes in LH secretion; whether this occurs in late pubertal obese girls is unknown. OBJECTIVE: The objective of the study was to test two hypotheses: 1) blunted day-to-night changes in LH secretion occur in both early and late pubertal obese girls, and 2) such alterations are specifically associated with hyperandrogenemia. DESIGN: This was a cross-sectional analysis. SETTING: The study was conducted at a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Twenty-seven early pubertal, premenarcheal girls (12 of whom were obese) and 63 late pubertal (postmenarcheal) girls (27 of whom were obese) participated in the study. INTERVENTION: Blood samples were taken every 10 minutes from 7:00 pm to 7:00 am. MAIN OUTCOME MEASURE: Change in LH pulse frequency [LH interpulse interval (IPI)] from daytime hours (7:00 pm-11:00 pm, while awake) to nighttime hours (11:00 pm to 7:00 am, while generally asleep). RESULTS: Both nonobese and obese postmenarcheal girls demonstrated significant day-to-night decreases in LH pulse frequency (IPI increases of 33% and 16%, respectively), but day-to-night changes were blunted in obese girls (P = .004, obese vs nonobese). Day-to-night LH pulse frequency decreased significantly in postmenarcheal obese subjects with normal T concentrations (26% IPI increase) but not in those with hyperandrogenemia. Similar differences were evident for LH pulse amplitude. Nonobese and obese early pubertal girls exhibited nonsignificant differences in day-night LH pulse frequency (day to night IPI increase of 26% vs decrease of 1%, respectively). CONCLUSIONS: Day-to-night changes in LH pulse secretion are blunted in postmenarcheal obese adolescent girls. This phenomenon may in part reflect hyperandrogenemia.

Neuroendocrine dysfunction in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common disorder characterized by ovulatory dysfunction and hyperandrogenemia (HA). Neuroendocrine abnormalities including increased gonadotropin-releasing hormone (GnRH) pulse frequency, increased luteinizing hormone (LH) pulsatility, and relatively decreased follicle stimulating hormone contribute to its pathogenesis. HA reduces inhibition of GnRH pulse frequency by progesterone, causing rapid LH pulse secretion and increasing ovarian androgen production. The origins of persistently rapid GnRH secretion are unknown but appear to evolve during puberty. Obese girls are at risk for HA and develop increased LH pulse frequency with elevated mean LH by late puberty. However, even early pubertal girls with HA have increased LH pulsatility and enhanced daytime LH pulse secretion, indicating the abnormalities may begin early in puberty. Decreasing sensitivity to progesterone may regulate normal maturation of LH secretion, potentially related to normally increasing levels of testosterone during puberty. This change in sensitivity may become exaggerated in girls with HA. Many girls with HA-especially those with hyperinsulinemia-do not exhibit normal LH pulse sensitivity to progesterone inhibition. Thus, HA may adversely affect LH pulse regulation during pubertal maturation leading to persistent HA and the development of PCOS.