Latest Hormone Replacement Journal Review

May 28, 2012 — Menopausal hormone therapy (HRT) reduced risk of fractures but increased risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence, according to a systematic review of articles published after 2002. Whereas estrogen alone decreased the risk for breast cancer, estrogen plus progestin increased risk for probable dementia and breast cancer. This new review, published online May 29 in the Annals of Internal Medicine, will be used to update the US Preventive Services Task Force recommendations.

"Menopausal hormone therapy to prevent chronic conditions is currently not recommended because of its adverse effects," write Heidi D. Nelson, MD, MPH, from the Oregon Health & Science University in Portland, and colleagues.

"The current indications for use from the U.S. Food and Drug Administration include short-term treatment of menopausal symptoms, such as vasomotor hot flashes or urogenital atrophy, and prevention of osteoporosis."

For the systematic review, Dr. Nelson and colleagues searched MEDLINE for articles published from January 2002 to November 2011, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews through the third quarter of 2011, Scopus, and bibliographies of retrieved articles. They limited inclusion to studies that were randomized, placebo-controlled trials of menopausal hormone therapy; evaluation of primary prevention of chronic conditions; and English-language publication since 2002.

Data were extracted regarding participants, study design, analysis, follow-up, and findings. Using established criteria, 2 investigators independently rated study quality.

The investigators identified 9 fair-quality trials meeting the inclusion criteria. Most of the findings came from the Women's Health Initiative (WHI), with 11 years of follow-up and collection of data most relevant to postmenopausal American women.

In the WHI, estrogen plus progestin therapy was associated with 46 fewer fractures per 10,000 woman-years. However, women taking HRT had an increased risk for invasive breast cancer (8 more per 10,000 woman-years), stroke (9 more per 10,000 woman-years), deep venous thrombosis (12 more per 10,000 woman-years), pulmonary embolism (9 more per 10,000 woman-years), lung cancer death (5 more per 10,000 woman-years), gallbladder disease (20 more per 10,000 woman-years), dementia (22 more per 10,000 woman-years), and urinary incontinence (872 more per 10,000 woman-years).

The risk for breast cancer was greater in women who previously used oral contraceptives or menopausal estrogen plus progestin therapy, or who were current smokers.

Estrogen-only therapy reduced the risk for several adverse outcomes, including fracture (56 fewer per 10,000 woman-years), invasive breast cancer (8 fewer per 10,000 woman-years), and mortality (2 fewer per 10,000 woman-years). However, the treatment increased risks for stroke (11 more per 10,000 woman-years), deep venous thrombosis (7 more per 10,000 woman-years), gallbladder disease (33 more per 10,000 woman-years), and urinary incontinence (1271 more per 10,000 woman-years).

The investigators could not identify subgroups based on age or comorbid conditions in which outcomes of menopausal HRT were consistently different.

Limitations of this review included those inherent in the trials themselves, such as low adherence, high dropout rate, insufficient power to detect risks for some outcomes, and assessment of few regimens.

"Continuing research is needed on such long-term outcomes as cancer and death to fully understand the implications of hormone therapy," the reviewers conclude.

The Agency for Healthcare Research and Quality funded this study and has financial relationships with some of its authors. Disclosures can be viewed at on the journal's Web site .

Ann Intern Med. Published online May 29, 2012. Full text


Menopause, or the permanent end of menstruation and fertility, is a natural biological process, not a medical illness. Even so, the physical and emotional symptoms of menopause can disrupt your sleep, sap your energy and — at least indirectly — trigger feelings of sadness and loss.

Hormonal changes cause the physical symptoms of menopause, but mistaken beliefs about the menopausal transition are partly to blame for the emotional ones. First, menopause doesn't mean the end is near — you've still got as much as half your life to go. Second, menopause will not snuff out your femininity and sexuality. In fact, you may be one of the many women who find it liberating to stop worrying about pregnancy and periods.

Most important, even though menopause is not an illness, you shouldn't hesitate to get treatment if you're having severe symptoms. Many treatments are available, from lifestyle adjustments to hormone therapy.

Technically, you don't actually "hit" menopause until it's been one year since your final menstrual period. In the United States, that happens about age 51, on average.

The signs and symptoms of menopause, however, often appear long before the one-year anniversary of your final period. They include:

    * Irregular periods

    * Decreased fertility

    * Vaginal dryness

    * Hot flashes

    * Sleep disturbances

    * Mood swings

    * Increased abdominal fat

    * Thinning hair

    * Loss of breast fullness

Menopause begins naturally when your ovaries start making less estrogen and progesterone, the hormones that regulate menstruation. The process gets under way in your late 30s. By that time, fewer potential eggs are ripening in your ovaries each month, and ovulation is less predictable. Also, the post-ovulation surge in progesterone — the hormone that prepares your body for pregnancy — becomes less dramatic. Your fertility declines, perhaps partially due to these hormonal effects.

These changes are more pronounced in your 40s, as are changes in your menstrual pattern. Your periods may become longer or shorter, heavier or lighter, and more or less frequent. Eventually, your ovaries shut down and you have no more periods. It's possible, but very unusual, to menstruate every month right up to your last period. You're much more likely, though, to have a gradual tapering off.

Unfortunately, there's no way to know exactly which period will be your last. You have to wait until well after the fact — 12 months after, by official definition. In your final months before reaching menopause, it's still possible to get pregnant, but it's quite unlikely.

Because this process takes place over years, menopause is commonly divided into the following two stages:

    * Perimenopause. This is the time you begin experiencing menopausal signs and symptoms, even though you still menstruate. Your hormone levels rise and fall unevenly, and you may have hot flashes and other symptoms. Perimenopause may last four to five years or longer.

    * Postmenopause. Once 12 months have passed since your last period, you've reached menopause. Your ovaries produce much less estrogen and no progesterone, and they don't release eggs. The years that follow are called postmenopause.