This week’s article discusses the correlation between low ovarian reserve and bone density. From a Chinese perspective this makes sense, especially when women are experiencing hot flashing (HF) and night sweating (NS). These two symptoms are commonly found in the kidney yin deficiency pattern. The kidney energy is the primary source of reproductive reserves. Just like a car, we have a tank of energy and if we travel too far without fueling up, the energy can run out. That tank of energy is found in the kidneys and as the tank starts to get low the emergency light comes on in the form of HF and NS. Symptoms, such as poor sleep, HF, NS, lack of ovulation, scanty menses and facial flushing are telling the women the reserves are low. When the warning signals are ignored the lowered energy will continue to deplete the kidneys and thus bone density can be lowered. Of course not all women with kidney yin deficiency will have lowered bone density, they may develop issues around fibroids, constipation or palpations. The beautiful part of Chinese medicine is its ability to see each person and their pattern of imbalance. Though for most women the common effect of kidney yin deficiency is heat and consumption of fluids – thus burning away the moisture and internal structure of the body (that’s way older women often look dry and hunched over) and thus the structure of the bones. It’s great to see Western medicine is interested in being proactive and understanding how to diagnosis women with low bond density before it is much harder to treat. If anything, I now realize the importance of educating my POF women about possible bone density problems and how to prevent future issues with supplementation.
Vasomotor symptoms in infertile premenopausal women: a hitherto unappreciated risk for low bone mineral density
Lubna Pal, M.B., B.S., John Norian, M.D.Gohar Zeitlian, M.D. , Kris Bevilacqua, Ph.D., Ruth Freeman, M.D Nanette Santoro, M.D. Volume 90, Issue 5, Pages 1626-1634 (November 2008) Fertility and Sterility,
Vasomotor symptoms (VMS), that is, hot flashes (HF) and night sweats (NS), a hallmark of perimenopause are not uncommonly encountered in the premenopausal period. Elevations in serum levels of FSH, a hallmark of reproductive aging, predate these clinical stigmata of perimenopause. Both elevations in the pituitary gonadotropins and declining serum E2 levels are suggested to play a pathogenic role in the occurrence of VMS.
Skeletal health is intimately related to and influenced by gonadal function. Bone mineral density (BMD) and bone metabolism or turnover has been shown to be independent predictors of risk for fracture. Limited data accrued in the perimenopausal and postmenopausal populations suggest an association between VMS and reduced BMD. The occurrence and the frequency of VMS have been shown to associate with low BMD and rapid deterioration in BMD in postmenopausal and perimenopausal women.
In the era of assisted reproduction, elevations in early follicular phase FSH and decline in inhibin B levels have emerged as reliable markers of declining ovarian reserve. Although testing for ovarian reserve constitutes an integral component of infertility workup, it is yet uncommonly used beyond this context, at least in the premenopausal years. Thus, infertile, yet healthy, premenopausal women constitute an optimal population for studying the relationship between VMS, ovarian reserve, and BMD status. Emerging literature suggests an association between elevations in FSH levels and bone loss, highlighting a potential mechanism for bone loss in the setting of declining ovarian reserve and the important for ovarian reserve testing and the implication of skeletal health.
This study explores the hypothesis that premenopausal and infertile women experiencing VMS will demonstrate evidence of both low BMD and poor ovarian reserve and will demonstrate biochemical evidence of enhanced bone turnover (i.e., elevated levels of markers of bone resorbption and formation) compared with those without these symptoms.
Results
Eighty-nine premenopausal women with infertility were enrolled over a 3-year period; 82 underwent BMD assessment. Of the 88 of the 89 patients in whom one or more contributory etiologies for infertility clearly were identified from the patient records, a single etiology for infertility was not diagnosed in 74. The commonest contributors to infertility were ovulatory disturbances, diminished ovarian reserve, followed by unexplained infertility, tubal infertility, and miscellaneous causes.
Responses for VMS were available for 75 of 89 of the participants; 9 of the participants acknowledged experiencing one or both of the specified VMS (NS only in 2/9, HF only in 3/9, or both NS and HF in 4/9). The frequency of VMS was described as “once or twice a day” by all those who were symptomatic. 73 participants answered to the query regarding “disturbed sleep.”
Although the distribution of infertility etiologies was comparable in the symptomatic vs. asymptomatic women, women with unexplained infertility were significantly more likely to specifically report NS.
Those experiencing VMS were nine times more likely to report sleep disturbances. The symptomatic group of women demonstrated evidence of poorer ovarian reserve, higher levels of FSH and E2, and lower inhibin B level; however, did not reach statistical significance.
Bone Mineral Density
Of the 82 enrollees for whom BMD measurements were available, responses about VMS were completed by 73. 19 of the premenopausal infertile women demonstrated evidence of LBMD.
Patients experiencing VMS demonstrated lower BMD scores. A significantly higher proportion of premenopausal women experiencing VMS demonstrated evidence of LBMD compared with those without these symptoms. This association with LBMD was most robust for NS, followed by VMS and HF.
Bone Metabolism
Bone metabolism, as reflected by the levels of markers of bone formation (BAP) and resorption (NTX, TRAP) as well as specifically by the cumulative turnover score, was noted to correlate inversely with patient’s age.
A relationship between enhanced bone turnover (reflected by higher levels of bone markers) and worsening ovarian reserve was noted; maximal FSH levels were observed to significantly correlate with TRAP and with the composite turnover score.
Discussion
Elevations in serum FSH levels are a hallmark of the period of perimenopause. Recent reports have provided evidence of direct effects of FSH on osteoclasts.
A decline in estrogen levels is suggested as a biological mechanism that contributes to VMS. Significantly lower circulating levels of E2 and its metabolites have been reported in women experiencing NS, and NS are considered the more profound of the two VMS. Hypoestrogenic may explain the observed relationship between VMS and LBMD. Although the symptomatic patients in our study demonstrated evidence of lower ovarian reserve, that is, lower levels of inhibin B and higher levels of FSH and smaller ovarian dimensions, the early follicular phase E2 levels actually were higher in the symptomatic women. This latter finding is of interest because higher E2 levels in the early follicular phase are recognized as a marker of declining ovarian reserve. We conjecture that poorer ovarian reserve in premenopausal women experiencing VMS is a plausible mechanism that can explain the occurrence of VMS as well as the low BMD in the setting of elevated bone turnover.
These young women will enter menopause with a lower so-called skeletal reserve, which then is destined to further decline during the early postmenopausal years. Our findings of LBMD and elevated bone turnover in premenopausal women experiencing VMS support that increased bone turnover may be a contributor to the low bone mass in these young women.
In summary, our findings provide evidence that VMS in premenopausal years can cause adverse health implications. Specifically, infertile women experiencing VMS (especially NS) and disturbed sleep demonstrate low BMD and enhanced bone turnover, which is unappreciated in such a young population of otherwise healthy women. These findings underscore the intimate relationship between reproductive health and bone metabolism in the premenopausal years. We believe that these data will help clinicians in offering appropriate patient screening and counseling that is aimed at strategies to stabilize osseous integrity as well as minimize adverse influences on the skeletal as well as reproductive health.