Steroidal contraceptive use is associated with lower bone mineral density in polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common condition affecting reproductive-aged women with features including hyperandrogenism and menstrual irregularity frequently treated with hormonal steroidal contraceptives. Women with PCOS appear to have lower bone mineral density (BMD). While steroidal contraceptives may positively affect bone health, their effect on BMD in PCOS is not known. The aim of this study was to assess BMD in women with PCOS according to recent contraceptive use. A cross-sectional analysis of 95 pre-menopausal overweight or obese sedentary women with PCOS [age 29.4 ± 6.4 years, body mass index (BMI) 36.1 ± 5.3 kg/m(2)] who either recently took steroidal contraceptives (ceased 3 months prior) or were not taking steroidal contraceptives was conducted. Clinical outcomes included BMD, anthropometry, insulin, glucose, reproductive hormones, dietary intake and vitamin use. BMD was significantly lower for women who used contraceptives compared to those who did not (mean difference 0.06 g/cm(2) 95 % confidence interval -0.11, -0.02, p = 0.005). In regression models, lower BMD was independently associated with contraceptive use (β = -0.05, 95 % CI -0.094, -0.002, p = 0.042), higher testosterone (β = -0.03, 95 % CI -0.05, -0.0008, p = 0.043) and lower BMI (β = 0.006, 95 % CI 0.002, 0.01, p = 0.007) (r (2) = 0.22, p = 0.001 for entire model). We report for the first time that overweight and obese women with PCOS with recent steroidal contraceptive use had lower BMD in comparison to non-users independent of factors known to contribute to BMD. Whether this observation is directly related to steroidal contraceptive use or other factors requires further investigation.

Competing Factors Link to Bone Health in Polycystic Ovary Syndrome: Chronic Low-Grade Inflammation Takes a Toll

“…Along with central adiposity, our findings suggest that current oral contraceptive use may be independently linked to increased systemic inflammation. This is consistent with studies showing that treatment with oral contraceptives leads to increased CRP levels 37 , and their use in PCOS is associated with lower BMD 38 .…”

Effect of combined oral contraceptives on orthodontic tooth movement in a female rat model

“…39,40 In a group of obese women with polycystic ovary syndrome, those using steroidal contraceptives were found to have lower bone mineral density in comparison with the non-users. 41 The current study did not find a significant difference in alveolar bone mineral density between the oral contraceptive group and the control. This may be because the observation time of 28 days was not long enough to observe changes in bone density, or the masticatory force and other stimulating factors may conceal the changes in bone, if there were any, during this time period.…”

Effects of distinct Polycystic Ovary Syndrome phenotypes on bone health

“…Moreover, the contraceptive formulation in this study varied (in terms of androgenic, progestin and oestrogen) with each likely to have different effects on bone (141, 142). Finally, total BMD (as assessed in the aforementioned study) is regarded as a less sensitive marker of bone health than BMD at specific measurement sites (e.g., lumbar spine and femoral neck) (140). Therefore, the clinical significance of these findings should be examined further in randomised controlled trials with assessment of bone turnover markers and site-specific BMD at baseline and following steroidal contraceptive use versus placebo.…”

“…In PCOS, treatment with steroidal contraceptives is used to regularise menstrual cycles and lower free testosterone by increasing SHBG, which in theory may influence BMD (139). In a cross-sectional analysis from Australia of 95 premenopausal women with PCOS and overweight or obesity who either recently took steroidal contraceptives (stopped 3 months prior) or were not taking steroidal contraceptives, total BMD was 8% lower for women with recent steroidal contraceptives (140). Furthermore, lower BMD was demonstrated to be independently associated with contraceptive uses, lower BMI, and higher testosterone (but not age, multivitamin, calcium intake or vitamin D, HOMA-IR, calcium, and alcohol) (140).…”

“…In a cross-sectional analysis from Australia of 95 premenopausal women with PCOS and overweight or obesity who either recently took steroidal contraceptives (stopped 3 months prior) or were not taking steroidal contraceptives, total BMD was 8% lower for women with recent steroidal contraceptives (140). Furthermore, lower BMD was demonstrated to be independently associated with contraceptive uses, lower BMI, and higher testosterone (but not age, multivitamin, calcium intake or vitamin D, HOMA-IR, calcium, and alcohol) (140). These findings are surprising given that steroidal contraceptives are frequently used to promote BMD maintenance (in sex steroid deficient states) and hyperandrogenism is regarded as having a protective effect on bone in PCOS.…”