Hormonal mechanisms of menstrual disturbances, metabolic disorders and effects of oral contraceptives in female athletes

Abstract: Background: During the last decades the number of women participating in sports has increased dramatically. Although exercise has beneficial health effects for most of these women, we now realize that strenuous exercise may also have serious medical consequences. Menstrual dysfunction is common among athletes and the exact mechanisms are not known. The metabolic consequences of long-standing amenorrhea are serious including increased bone resorption and possibly deleterious effects on the cardiovascular system. Oral contraceptives (OCs) are often used for treatment of estrogen deficiency but there are no studies evaluating the effects of this treatment in athletes. The aims of this work were to study mechanisms of menstrual disturbances and associated metabolic disorders in endurance athletes. Furthermore, to evaluate effects of OCs on bone mineral density (BMD), endothelial function and physical performance in athletes. Methods: Age- and body mass index-matched groups of endurance athletes with menstrual disturbance, regularly cycling athletes and sedentary controls, all together 51 subjects, were examined before and after -10 months of treatment with a low-dose, monophasic, combined OC. Baseline hormonal status and diurnal profiles of pituitary hormones and steroid hormones were investigated. Body composition including BMD was examined by dual energy X-ray absorptiometry and physical performance was evaluated by endurance and strength tests. Blood lipids were analyzed and endothelial function was studied by ultrasound assessment of flow-mediated vasodilatation (FMD). Results: The majority of athletes with menstrual disturbance had a hormonal profile in accordance with hypothalamic inhibition of the reproductive system including decreased diurnal LH-pulsatility and peak amplitude of prolactin and increased diurnal secretion of cortisol and growth hormone. This group of athletes had the lowest fat mass and BMD among all groups. In addition, we identified a hyperandrogenic subgroup of athletes with menstrual disturbance, having increased diurnal secretion of testosterone, increased LH/FSH ratio and decreased serum levels of SHBG. This subgroup had an anabolic body composition with the highest total BMD and lean body mass among the groups. The hyperandrogenic subgroup also had the highest V02max and the highest performance values in general. Athletes with amenorrhea had impaired endothelial function and an unfavorable lipid profile, whereas oligomenorrheic athletes had the most favorable lipid profile and an intermediate FMD. OC treatment caused a significant change in weight and fat mass only in the athlete group with menstrual disturbance. OC treatment also increased BMD in athletes with the largest increase in those with a low BMD at baseline. Despite significant changes in body composition, only a small impact on physical performance was recorded during OC. Endothelial dysfunction in amenorrheic athletes was improved by OC treatment. Conclusions: Menstrual disturbances in female athletes are often explained as a consequence of hypothalamic inhibition due to energy deficiency. This thesis suggests essential hyperandrogenism, such as polycystic ovary syndrome as an alternative mechanism underlying menstrual disturbance in athletes, especially oligomenorrhea. This condition may imply an advantage for physical performance. Amenorrhea in athletes is associated with endothelial dysfunction and an unfavorable lipid profile. OC treatment has predominantly beneficial effects on body composition, BMD and endothelial function without adverse effects on physical performance and could be used for prevention of osteoporosis in athletic amenorrhea.