By Jeffrey T. Jensen, MD, MPH

Leon Speroff Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland

Dr. Jensen reports that he is a consultant for and receives grant/research support from Bayer, Merck, ContraMed, and FHI360; he receives grant/research support from Abbvie, HRA Pharma, Medicines 360, and Conrad; and he is a consultant for the Population Council.

SYNOPSIS: Postmenopausal hormone therapy may reduce the risk of developing age-related hyperkyphosis, commonly known as a “Dowager’s hump.” Such therapy may provide long-term benefits

SOURCE: Woods GN, Huang MH, Cawthon PM, et al. Patterns of menopausal hormone therapy use and hyperkyphosis in older women. Menopause 2018;25:738-743.

The abnormal exaggerated curvature of the dorsal spine with compensatory cervical lordosis that commonly occurs in elderly postmenopausal women is referred to colloquially as a “Dowager’s hump.” Medically, it is known as hyperkyphosis. Women with hyperkyphosis are at risk for other fragility health concerns, including poor physical function, falls, fractures, and early mortality. The risk factors for hyperkyphosis include low bone mineral density (BMD), bone loss, and vertebral fractures. Since menopausal hormone therapy (HT) reverses bone loss and prevents vertebral fractures, Woods et al hypothesized that use of HT would reduce the risk for developing hyperkyphosis. As an initial step to evaluate this hypothesis, they used data available from the Study of Osteoporotic Fractures (SOF), a longitudinal, multicenter, observational study of 9,704 community-dwelling ambulatory women ≥ 65 years of age recruited between 1986 and 1988 from four clinics in Baltimore; Minneapolis; Monongahela Valley, PA; and Portland, OR. Of these 9,704 women, the authors selected a random group of 1,063 women from a subset of participants with longitudinal follow-up (seven study visits) that detailed HT use spanning an average of 15 years and adequate spinal radiographs at baseline and at year 15 suitable for determination of a modified Cobb angle of kyphosis. The modified Cobb angle uses the anchors of T4 and T12 to measure the angle in lateral spine radiographs instead of T1 to T3, as the higher thoracic vertebral bodies typically are not well visualized on lateral X-rays (available in the SOF). Readers of the films were blinded to HT status.

Investigators relied on self-report during the study period to classify HT: continuous (current use reported at six or more of seven visits), 12% of sample; intermittent (current use reported at between one and five of seven visits), 17%; remote past (reported past use at study baseline but no current use at any visit), 24%; or never, 46%. Evaluation of the demographic characteristics of participants revealed no clinically important or statistically significant differences between HT pattern groups and age (overall mean at follow-up, 83.7 years), body weight, or family history of hyperkyphosis (26%).

Compared to never users (52.6°), continuous HT users had the smallest mean Cobb angle (48.9°), followed by remote past (49.9°) and intermittent use (51.5°). Consistent with this effect, users of continuous HT also had higher BMD (0.805 g/cm2) compared to never use (0.704 g/cm2), with a dose effect observed with intermittent (0.733 g/cm2) and remote past (0.715 g/cm2) use. The authors did not report statistical significance.

The differences in the Cobb angle with continuous and remote past use of HT were statistically significant in the age- and clinic-adjusted model (P = 0.01). In the fully adjusted model, which also included the number of prevalent vertebral fractures, family history of hyperkyphosis, the presence of degenerative disc disease, total hip BMD, and body weight, the strength of association decreased and became nonsignificant (only -2.8°; P = 0.06) for continuous use. Of interest, this full adjustment did not attenuate the beneficial association seen with remote past use (-2.8°; P = 0.02). The authors concluded that these results support a role for postmenopausal HT in the prevention of age-related hyperkyphosis.

COMMENTARY

At first glance, these results seem obvious. We know that low BMD, bone loss, and vertebral fractures are predictable consequences of menopause, and also are independent risk factors for hyperkyphosis. We also know that HT prevents postmenopausal bone loss, maintains or improves BMD, and prevents fracture.1,2 However, no one has evaluated whether HT can reduce the risk of developing hyperkyphosis.

Why study this question? The fact that we have a colloquial expression, “Dowager’s hump,” for the physical changes of spinal compression fractures and short stature that develop in elderly women reveals the ubiquity of the condition. But we also recognize hyperkyphosis as a fragility sign. While we cannot stop the aging process, I have not met any patient looking forward to the development of this physical change of fragility.

The results of this paper provide additional information useful in the counseling of perimenopausal and early postmenopausal women regarding HT. We now have evidence that the use of HT can reduce the risk of developing a Dowager’s hump. This may motivate some women to consider HT more carefully.

The cross-sectional design, simple cohort analysis, and lack of detail on type or dose of HT represent major weaknesses that must be considered in evaluating this research. However, notable strengths include the large sample size and prospective follow-up over 15 years. We see biologic plausibility in the results. Continuous use of HT resulted in the greatest reduction in Cobb angle (almost 4°). I am not bothered that this benefit attenuated and was no longer statistically significant after full adjustment. The full adjustment model included BMD and the presence of degenerative disk disease (DDD). Not surprising, continuous HT users had the highest BMD and the lowest rate of DDD, as HT also improved both findings. Thus, these characteristics are not confounders of the association of benefit of HT on the reduced Cobb angle. HT improves BMD and prevents DDD. We should expect correlation with the benefit through a causal relationship. Also, we should expect that adjusting for these factors would tend to attenuate the overall beneficial effect seen with respect to the Cobb angle.

I am intrigued by the fact that remote past users also showed a significant reduction in the Cobb angle, and that this benefit remained significant even after complete adjustment. The absence in change in the effect supports my previous comment that adjusting for the benefit in BMD diluted the effect seen with continuous use. In contrast to continuous users, the BMD of remote past users was similar to that of never users. Remote past users stopped HT prior to enrolling in the study (mean age, 68 years). This suggests that initiation of HT and strong protection against bone loss in the early postmenopausal years might provide lasting benefit, even if bone loss eventually catches up.

These results may provide clinicians with an additional counseling point to encourage healthy perimenopausal and postmenopausal women to consider initiation of HT as an early intervention. If a patient has reservations about the potential benefits of HT, perhaps these new results will push her over the “hump.”

REFERENCES

  1. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-333.
  2. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.