Vasomotor symptoms in infertile premenopausal women: a hitherto unappreciated risk for low bone mineral density

Objective: To identify the prevalence of vasomotor symptoms (VMS) in a population of premenopausal infertile women and to determine whether VMS is associated with enhanced bone turnover and low bone mineral density (BMD). Design: Cross-sectional study. Setting: Academic infertility practice. Patient(s): Eighty-two premenopausal infertile, but otherwise healthy, women attending for routine infertility care. Intervention(s): Bone mineral density testing, general health and Profile of Mood States questionnaires, and serum samples (cycle d 1-3). Main Outcome Measure(s): Vasomotor symptoms, specifically hot flashes (HF) and night sweats (NS); BMD z score, BMD categorized as low (Z ≤ -1.0) or normal (Z > -1.0); ovarian reserve assessment (biochemical and ovarian dimensions on transvaginal ultrasound); and serum markers of bone turnover (collagen N-terminal telo-peptide, tartrate-resistant acid phosphatase, and bone-specific alkaline phosphatase) and ovarian reserve (FSH, E₂, and inhibin B). Multivariable regression analyses determined the associations between VMS, BMD, and bone turnover (individual markers and composite turnover score). Result(s): The prevalence of VMS was 12% in this relatively young population (mean [± SD] age [years], 34.53 ± 4.32). Symptomatic women were statistically significantly more likely to report sleep disturbances and to exhibit evidence of low BMD, as well as to exhibit enhanced bone turnover and poorer ovarian reserve parameters. Multivariable logistic regression analyses confirmed the statistical significance of both HF and NS as independent correlates to low BMD after adjusting for age, body mass index, smoking status, menstrual regularity, and ovarian reserve status. Multivariable linear regression analyses demonstrated that NS, but not HF, predicted higher bone turnover at a statistically significant level after adjusting for age, smoking, menstrual regularity, and ovarian reserve. Conclusion(s): We demonstrate, in a premenopausal population of infertile women, evidence of morbid accompaniments to VMS, including sleep disturbances and evidence of low BMD. Our data further suggest a state of enhanced bone turnover in association with VMS, specifically in those experiencing NS. Declining ovarian reserve may be the common pathophysiological mechanism underlying VMS and low BMD in the symptomatic population and merits further investigation.