EXECUTIVE SUMMARY

Women at the highest genetic risk for fractures may benefit most from hormone therapy, according to a new study.

  • The initiation of hormone therapy is considered an acceptable option for women up to 59 years of age or within 10 years of menopause and those who complain of moderate to severe menopausal symptoms.
  • Clinicians can use a fracture risk assessment tool to predict if a patient is at risk for bone fracture in the next 10 years. The tool is based on such risk factors as age, body mass index, history of fracture, daily alcohol intake, and whether a patient smokes, and suffers from rheumatoid arthritis or any other secondary causes of osteoporosis.

Women at the highest genetic risk for fracture may benefit the most from hormone therapy, according to data from a new study.1

Previous research has shown the protective effect of menopausal hormone therapy on bone.2 However, scientists from four institutions wanted to explore whether genetic susceptibility modifies the association of hormone therapy and fracture risk.

To conduct the current analysis, the team constructed two weighted genetic risk scores, based on 16 fracture-associated variants and 50 bone mineral density variants. The researchers included 9,922 genotyped white postmenopausal women ages 50-79 from the Women’s Health Initiative hormone therapy randomized trials in their analysis.

“We found that women who are genetically at the highest fracture risk can enjoy the greatest protection from fracture when they use hormone therapy,” says Heather Ochs-Balcom, PhD, head of the research team and associate professor of epidemiology and environmental health in the University at Buffalo’s School of Public Health and Health Professions.

Further studies on gene therapy interaction are needed to evaluate the advantages of targeted interventions based on genetic profiles, notes Youjin Wang, PhD, postdoctoral fellow at the National Cancer Institute’s clinical genetics branch. Wang, lead author of the paper, was a doctoral candidate in epidemiology and environmental health at the University at Buffalo.

Evaluate Risks, Benefits

In 2002, the Women’s Health Initiative reported an increased risk of breast cancer, heart disease, stroke, and blood clots with the use of combined estrogen plus progestin hormone therapy. In the years following those results, further research has indicated that the type of therapy (estrogen or estrogen plus progestin), how it is taken, and the timing of treatment initiation (pre- or post-menopause) produce different benefits and side effects.

The risk of side effects (such as heart attack, stroke, blood clot, or breast cancer) with hormone therapy in healthy women 50-59 years of age is low. In contrast, using hormone therapy for a long time or starting treatment when women are several years beyond menopause is associated with a higher risk of such side effects.3

The initiation of hormone therapy is considered an acceptable option for patients up to 59 years of age or within 10 years of menopause and healthy women who suffer from moderate to severe menopausal symptoms, according to a 2012 joint statement issued by the North American Menopause Society, the American Society for Reproductive Medicine, and the Endocrine Society.4

The World Health Organization (WHO) developed a fracture risk assessment tool called FRAX, which can help clinicians predict if a patient is at risk for bone fracture in the next 10 years. Clinicians can use FRAX to decide if a patient is at high risk for fracture if her initial scan indicates low bone mass. WHO built the tool using such risk factors as age, body mass index, history of fracture, daily alcohol intake, and whether a patient smokes, suffers from rheumatoid arthritis, or exhibits any other secondary causes of osteoporosis. (Access it at: http://bit.ly/2qeeb9d.)

The U.S. Preventive Services Task Force recommends screening women 65 years of age and older for osteoporosis, since gender and age are the leading risk factors. Younger women who present with certain risk factors, such as a small body frame, a history of fractures, or taking medication that thins bones, also should receive screening.5

Recent research indicates that too few women at high risk for osteoporosis undergo testing for the condition, while too many women at low risk receive screening.6

For women at risk of osteoporosis, providers can offer the following tips to patients to help them improve bone health:

  • Take medications to strengthen bones, and avoid medications that can weaken bones;
  • Consume a healthy diet rich in calcium and vitamin D;
  • Perform regular weight-bearing exercises;
  • Do not smoke;
  • Limit alcohol intake.

REFERENCES

  1. Wang Y, Wactawski-Wende J, Sucheston-Campbell LE, et al. Gene-hormone therapy interaction and fracture risk in postmenopausal women. J Clin Endocrinol Metab 2017; doi: 10.1210/jc.2016-2936. [Epub ahead of print].
  2. Papadakis G, Hans D, Gonzalez-Rodriguez E, et al. The benefit of menopausal hormone therapy on bone density and microarchitecture persists after its withdrawal. J Clin Endocrinol Metab 2016;101:5004-5011.
  3. North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012;19:257-271.
  4. Stuenkel CA, Gass ML, Manson, JE, et al. A decade after the Women’s Health Initiative - the experts do agree. J Clin Endocrinol Metab 2012;97:2617-2618.
  5. U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2011;154:356-364.
  6. Amarnath AL, Franks P, Robbins JA, et al. Underuse and overuse of osteoporosis screening in a regional health system: A retrospective cohort study. J Gen Intern Med 2015;30:1733-1740.