Clinical Review


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Here is a roundup of the latest data on vitamin D requirements in women and how the route, timing, and duration of hormone therapy influence its safety and efficacy




Dr. Kaunitz receives grant or research support from Bayer, Agile, Noven, Teva, and Medical Diagnostic Laboratories, is a consultant to Bayer, Merck, and Teva, and owns stock in Becton Dickinson.

Among the developments of the past year in the care of menopausal women are:

  • updated guidelines from the Institute of Medicine regarding vitamin D requirements—suggesting that fewer women are deficient in this nutrient than experts had believed
  • new data from Europe on hormone therapy (HT) that highlight the safety of transdermal estrogen in comparison with oral administration
  • a recent analysis from the Women’s Health Initiative (WHI), confirming a small elevated risk of breast cancer mortality with use of combination estrogen-progestin HT
  • confirmation that age at initiation of HT determines its effect on cardiovascular health
  • clarification of the association between HT and dementia
  • new data demonstrating modest improvement in hot flushes when the serotonin reuptake inhibitor (SRI) escitalopram is used
  • a brand new report from the WHI estrogen-alone arm that shows a protective effect against breast cancer.

The new data on HT suggest that we still have much to learn about its benefits and risks. We also are reaching an understanding that, for many young, symptomatic, menopausal patients, HT can represent a safe choice, with much depending on the timing and duration of therapy.

For more on how your colleagues are managing menopausal patients with and without hormone therapy, see “Is hormone therapy still a valid option? 12 ObGyns address this question,” on the facing page.

Menopausal women need less vitamin D than we thought

Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: IOM; December 2010. Accessed March 24, 2011.

In the 2010 Update on Menopause, I summarized recent findings on vitamin D requirements, including recommendations that menopausal women should take at least 800 IU of vitamin D daily. I also described the prevailing expert opinion that many North American women are deficient in this nutrient.

What a difference a year can make! In late November, the Institute of Medicine (IOM) released a comprehensive report on vitamin D. Here are some of its conclusions:

  • Vitamin D plays an important role in skeletal health but its role in other areas, including cardiovascular disease and cancer, is uncertain
  • An intake of 600 IU of vitamin D daily is appropriate for girls and for women as old as 70 years; an in-take of 800 IU daily is appropriate for women older than 70 years
  • A serum level of 25-hydroxy vitamin D of 20 ng/mL is consistent with adequate vitamin D status; this is lower than the threshold many have recommended
  • With few exceptions, all people who live in North America—including those who have minimal or no exposure to sunlight—are receiving adequate calcium and vitamin D
  • Ingestion of more than 4,000 IU of vitamin D daily can cause renal damage and injure other tissues.

The IOM report will likely prompt multivitamin manufacturers to increase the amount of vitamin D contained in their supplements to 600 IU daily. In addition, the report will probably discourage the common practice of checking serum 25-hydroxy vitamin D levels and prescribing a high dosage of vitamin D supplementation when the level is below 30 ng/mL.


I continue to recommend multivitamin supplements that include calcium and vitamin D (but no iron) to my menopausal patients. However, I no longer routinely recommend that they take additional calcium and vitamin D or undergo assessment of serum vitamin D levels.

Is transdermal estrogen safer than oral administration?

Canonico M, Fournier A, Carcaillon L, et al. Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism: results from the E3N cohort study. Arterioscler Thromb Vasc Biol. 2010;30(2):340–345.

Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519. doi: 10.1136/bmj.c2519.

In the WHI, the combination of oral conjugated equine estrogen and medroxyprogesterone acetate more than doubled the risk of deep venous thrombosis and pulmonary embolism and modestly increased the risk of stroke, compared with nonuse.1

A year after publication of the initial findings of the WHI estrogen-progestin arm, the Estrogen and THromboEmbolism Risk Study Group (ESTHER) case-control study from France provided evidence that transdermal estrogen does not increase the risk of venous thrombosis.2 In France, many menopausal women use HT, and the transdermal route of administration is common.


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