EXECUTIVE SUMMARY

A new analysis of data from the Women’s Health Initiative trial indicates an increased risk of fracture among women who reported early menopause (age 40 or younger), regardless of whether they were treated with hormone therapy and/or calcium and vitamin D supplementation.

  • Based on an evaluation of nearly 22,000 women included in the trials, women younger than age 40 already in menopause demonstrated significantly higher risks for fracture than women who experienced menopause between the ages of 40 and 49 or after 50, regardless of treatment intervention.
  • Providers should consider a woman’s age at menopause onset when evaluating patients for fracture risk, data indicate.

A new analysis of data from the Women’s Health Initiative (WHI) trial indicates an increased risk of fracture among women who reported early menopause (age 40 or younger), regardless of whether they were treated with hormone therapy and/or calcium and vitamin D supplementation.1 Although previous findings from the WHI trial indicated that menopause before the age of 40 led to higher fracture risk,2 these new findings suggest that even with calcium and vitamin D supplements, risk of fracture remains high.

Based on an evaluation of nearly 22,000 women included in the WHI trials, women younger than age 40 already in menopause had significantly higher risks for fracture than women who experienced menopause between the ages of 40 and 49 or after 50, regardless of treatment intervention, data indicate.

Clinicians traditionally have counseled for calcium and vitamin D intake to increase bone mineral density. Estrogen users in the initial WHI study demonstrated reductions in vertebral and hip fractures that were comparable in magnitude to drops in fractures seen with other agents.2 Scientists designed the current analysis to evaluate the effectiveness of calcium, vitamin D, and/or hormones in offsetting the higher fracture risks for women experiencing early menopause.

“This study highlights the need for healthcare providers to take into consideration a woman’s age at menopause onset when evaluating patients for fracture risk,” says JoAnn Pinkerton, MD, executive director of the North American Menopause Society in Cleveland.

Women at risk for bone loss need 1,200 mg of calcium per day, with adequate vitamin D, and should be encouraged to get as much as possible through diet due to concern that too much supplemental calcium may increase atherosclerotic plaque in women, Pinkerton notes. Providers also should evaluate whether women with early menopause are candidates for hormone replacement.

Women who have early menopause are at greater risk of fracture, observes Susan Wysocki, WHNP-BC, FAANP, president & CEO of iWomansHealth in Washington, DC, which focuses on information on women’s health issues for clinicians and consumers. Regardless of the fact that the study showed that interventions such as calcium, vitamin D supplements, and hormone therapy did not make a difference in their risk, it does not mean that these interventions should not be offered, Wysocki notes.

“Rather, women who have experienced early menopause should be made aware that their risk of fracture is higher so they can take appropriate action for their future,” she states.

Review The Data

For this study, researchers compared the hazard ratios for any fracture among more than 20,000 healthy postmenopausal women ages 50-79 years enrolled in the WHI clinical trial who reported nonsurgical menopause at three age points: younger than age 40, ages 40-49, and age 50 or older.

Women were combined into arms according to whether they received hormone therapy only, calcium/vitamin D supplementation, hormone therapy plus calcium/vitamin D supplementation, or placebo.

Overall, women in the placebo group demonstrated a higher risk of fracture than those receiving treatment with hormone therapy and/or calcium/vitamin D; the effect of treatment as predictor of reduced fracture was significant (P = 0.004).

However, treatment did not change the previously identified relationship between early age at menopause and risk of fracture. About one-fifth of women who experienced menopause before age 40 experienced fracture, regardless of treatment modality, compared with 14% of treated women who experienced menopause at age 50 or later. The analysis found a higher hazard ratio (30-35%) for any fracture in women who reported early menopause, than for women who reported menopause later (hazard ratio, 1.30-1.36 for fracture when menopause at age below 40 vs. age 40-49 and age 50 and over, respectively). Scientists were unable to determine whether menopause age altered risk for any particular type of fracture since absolute numbers for each fracture type were so small.

They also were unable to determine whether the cause of fracture was traumatic or resulting from osteoporosis.1

Discuss Bone, Dental Health

Estrogen is required by both males and females for optimal bone health; the significant decline in estrogen levels at menopause triggers a time-limited rapid bone loss in women not seen in men.4 Osteoporosis in postmenopausal women also has been linked to tooth loss, notes Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences in Pomona, CA. Clinicians also should discuss this with patients, she says.

The same processes that lead to loss of bone in the spine and hips also can lead to loss of the alveolar bone of the jaws, resulting in periodontal disease, loose teeth, and tooth loss.5 The rate of bone loss in postmenopausal women predicts tooth loss. Data indicate that for every 1% per year drop in whole-body bone mineral density, the risk of tooth loss increases more than four times.6

In addition to discussion of calcium, vitamin D, and potential hormone therapy, women should be counseled about lifestyle factors that may affect bone density and fracture risk, including smoking, poor nutrition, excessive weight loss, weight-bearing and muscle-strengthening exercise, and fall prevention measures.4

REFERENCES

  1. Sullivan SD, Lehman A, Nathan NK, et al. Age of menopause and fracture risk in postmenopausal women randomized to calcium + vitamin D, hormone therapy, or the combination: Results from the Women’s Health Initiative Clinical Trials. Menopause 2016; doi:10.1097/GME.0000000000000775.
  2. Sullivan SD, Lehman A, Thomas F, et al. Effects of self-reported age at nonsurgical menopause on time to first fracture and bone mineral density in the Women’s Health Initiative Observational Study. Menopause 2015;22:1035-1044.
  3. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin for healthy postmenopausal women. JAMA 2002;288:321-333.
  4. American College of Obstetricians and Gynecologists. Osteoporosis. Practice Bulletin No. 129. Obstet Gynecol 2012;120:718-734.
  5. Buencamino MCA, Palomo L, Thacker HL. How menopause affects oral health, and what we can do about it. Cleveland Clin J Med 2009;76:467-475.
  6. Krall EA, Garcia RI, Dawson-Hughes B. Increased risk of tooth loss is related to bone loss at the whole body, hip and spine. Calcif Tissue Int 1996;59:433-437.