Negative Spinal Bone Mineral Density Changes and Subclinical Ovulatory Disturbances—Prospective Data in Healthy Premenopausal Women With Regular Menstrual Cycles

Abstract

Subclinical ovulatory disturbances (anovulation or short luteal phases within normal-length menstrual cycles) indicate lower progesterone-to-estrogen levels. Given that progesterone plays a bone formation role, subclinical ovulatory disturbances may be associated with bone loss or less than expected bone gain. Our purpose was to perform a meta-analysis of prospective studies in healthy premenopausal women to determine the overall relationship of subclinical ovulatory disturbances to change in bone mineral density. Two reviewers independently identified from serial literature searches 6 studies meeting inclusion criteria: a 2-year study in 114 young adult women, 2006-2009, Vancouver, Canada; a 2-year study in 189 premenopausal women, 2000-2005, Toronto, Canada; a single-cycle study in 14 young women, 1996-1997, Melbourne, Australia; an 18-month study in 53 women, 1990-1995, Santa Clara, California; a 4-year study in 27 women, 1988-1995, Vancouver, Canada; and a 1-year study in 66 women, 1985-1988, Vancouver, Canada. This meta-analysis included a combined sample size of 473 observations in 436 premenopausal women studied over 1-4 years and aged 14-47 years. The percentage of women with ovulatory disturbances varied significantly from 13% to 82%. Women with more frequent ovulatory disturbances had more negative percentage changes in spine bone mineral density (weighted mean difference = -0.86; P = 0.040) for random-effects analysis. There was significant heterogeneity among these 6 studies (I(2) = 80%). In summary, these data show that regularly menstruating women with more frequent ovulatory disturbances experience more negative changes in bone (approximately -0.9% per year). These cycles with silent estrogen/progesterone imbalance may be clinically important.

Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction

“…Thus, no apparent or physical indication of a menstrual disturbance occurred, and subtle menstrual disturbances were detected exclusively by the measurement of urinary metabolites of menstrual cycle hormones. Consequently, exercising women may be experiencing subtle forms of menstrual dysfunction secondary to an energy deficit but may not be aware of such disturbances or the potential impact of these disturbances on fertility and bone health (13,18,24).…”

The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S)

“…Oestrogen increases uptake of calcium into blood and deposition into bone, while progesterone facilitates the actions of oestrogen through multiple complex mechanisms 34. Even silent oestrogen/progesterone imbalance, as seen in subclinical ovulatory disturbances with low EA may produce negative changes in bone 35. In men and women, testosterone has anabolic effects on bone, stimulating osteoclasts and increasing bone formation and calcium absorption 36.…”

Comparison of Site-Specific Bone Mineral Densities between Endurance Runners and Sprinters in Adolescent Women

“…Several parameters were not evaluated, such as bone metabolism markers, sex hormones (e.g., estrogen and progesterone), and reproductive maturation (such as tanner breast stage). Moreover, a previous study reported that subclinical ovulatory disturbance provides negative effect on bone [29]; however, the present study did not assess that. Low-dose oral contraceptives may impair the attainment of peak bone mass [30].…”