Acute effects of oral contraceptives on markers of bone turnover and cytokines in women with exercise associated menstrual dysfunction

Date of Completion

January 2006


Health Sciences, Obstetrics and Gynecology|Health Sciences, Recreation




Menstrual dysfunction has been reported to occur in up to 60% of premenopausal women who are physically active and is most likely the result of an energy deficit. The associated hypoestrogenism has a negative impact on bone health by decreasing bone mineral density. Several osteotropic cytokines have been shown to regulate bone cell differentiation, activation and apoptosis in cell culture models. Estrogen provides an inhibitory effect on some cytokines (e.g., TNF-α, M-CSF) and stimulatory effect on others (e.g., OPG, IFN-γ). In the face of an energy deficit the resumption of regular menses is unlikely, thus alternative strategies are necessary to help minimize the effects of estrogen deficiency on the skeleton. Prescribing oral contraceptive (OC) therapy is standard clinical practice by physicians to remedy the menstrual dysfunction and presumably help protect the skeleton. Recent advances in biochemical markers have provided the opportunity to examine the impact of OCs on skeletal metabolism. Only one short term (less than 3 months) study has investigated the effects of OC therapy on bone metabolism in premenopausal women with hypothalamic amenorrhea. They reported a reduction in bone formation and resorption markers after three months. To date, no study has examined the response of osteotropic cytokines to OC therapy in premenopausal women with exercise associated menstrual dysfunction (EAMD). Therefore, the purpose of this study was to examine the impact of one cycle of OCs on markers of bone formation and resorption in addition to osteotropic cytokines in premenopausal women with EAMD. A secondary aim was to determine the relationship between changes in bone markers and osteotropic cytokines. Six women 18-25 years of age participated in an eight week prospective intervention. Subjects received daily vitamin D and calcium supplements throughout the study and were provided with one 28-day cycle of Ortho Tri-Cyclen LO ® after four weeks of the supplemental run-in phase. Blood samples were taken at Baseline, 4 Week Supplement, Mid OC + Supplement, and End OC + Supplement. After two weeks of OC sCTx was suppressed (43%, p = 0.027) and there was a trend for PIMP to be suppressed (32%, p = 0.06). There was a slight rebound during the final two weeks of OC, but the bone markers remained suppressed at End OC + Supplement compared to Baseline (∼20%). Although there was an increase in IFN-γ (20%) and TNF-α (133%) after four weeks of OC therapy, there were no statistically significant changes in any of the osteotropic cytokines. Unique relationships were observed between TNF-α and IFN-γ with bone turnover. Specifically, the change in TNF-α accounted for 66% of the variance for the change in PINP and the change in IFN-γ accounted for 41% of the variance for the change in sCTx during the first two and final two weeks of OC therapy, respectively. Oral contraceptives rapidly suppressed bone turnover in premenopausal women with EAMD, still the measurement of systemic cytokines requires additional research to determine the utility of their use in monitoring therapeutic interventions targeting skeletal metabolism in women with EAMD.^