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Thursday, April 29, 2010

My Take on Postmenopausal Hormone Replacement Therapy

During the past several months postmenopausal hormone replacement has resurfaced as a topic of discussion.

On April 12th The New York Times published an article written by Cynthia Goran reviewing current controversies in post-menopausal hormone replacement therapy, told from the point of view of patient-investigator.

The article, as discussed nicely by health blogger Margaret Polaneczky, tells of the so call “window hypothesis” of estrogen therapy. The premise is that reported risks of adverse effects from hormone replacement therapy (HRT) cannot be generalized from older menopausal women to younger menopausal woman. There may be some truth to this argument.

In March 2010 the North American Menopause Society (NAMS) revised its 2008 consensus statement. The 2010 evidence-based review was performed by an Advisory Panel of clinicians and researchers in the field of women’s health. The Position Statement on treatment of menopause generally looks similar to the 2008 recommendations.

Currently postmenopausal hormone replacement therapy is not advised for routine use for preventive purposes in postmenopausal women. These recommendations are in large part based on the largest randomized controlled trial (RCT) to date on hormone replacement therapy in postmenopausal women, the Women’s Health Initiative (WHI). Since the July 2002 press release from the estrogen and progesterone arm of this study reporting the negative effects of hormone replacement therapy, post-menopausal HRT use has declined substantially. This largest RCT of HRT to date of 16,000 postmenopausal women found that oral estrogen use combined with progesterone (required for women with a uterus) was associated with increased rates of carcinoma of the breast and cardiovascular risk, including increased risk of stroke. The magnitude of the breast cancer risk reported was 8 additional breast cancers per 10,000 women, or a 24% increase in breast cancer risk.

For a nice summary of the WHI findings and associated risks see Menopause Fact Sheet

In March 2004 the estrogen alone trial of the WHI was reported. This study looked at oral estrogen use (.625 mg daily) in women who did not require progesterone, as they had undergone hysterectomy. “Unopposed” estrogen (without progesterone) is a known clear risk factor for uterine cancer. This arm reported on 11,000 women who were noted to have increased stroke risk, though were not found to have increased breast cancer risk.

The dispute over the applicability of the WHI findings stems from the fact that the average age of women studied was 63 years and the average time from menopause was >10 years. More recent analysis of younger subgroups of women, closer to the time of menopause, have in fact shown decreased cardiovascular risk with HRT. Additional study has shown that younger menopausal women treated with HRT have less coronary calcium build-up (linked to cardiovascular risk) than those randomized to placebo. These data form the basis for the “window,” or timing hypothesis that HRT may be cardioprotective when initiated earlier.

Needless to say this does not negate the finding that the combination of oral conjugated estrogen (.625 mg) and oral progesterone, medroxy-progesterone (2.5-5 mg), has been found to increase breast cancer risk in postmenopausal users, regardless of timing, when used for more than 3 to 5 years. In addition, HRT, both estrogen alone and estrogen with progestin, puts women at risk for abnormal mammograms and breast procedures.

Currently, the main indication for postmenopausal HRT is for treatment of vasomotor symptoms (hot flashes and night sweats). For this purpose HRT is the most effective treatment available and is recommended for no more than 5 years of use. HRT is also effective for treatment and prevention of osteoporosis, though is not recommended for either as first line therapy given its known risks.

Other news of interest on postmenopausal hormone replacement:
  • Transdermal estrogen has different biochemical effects, and therefore may have a better safety profile than oral estrogen.
  • There is not evidence to support the use of progesterone based intrauterine devices (Mirena) to prevent the endometrial hyperplasia related to estrogen use.
  • There is also not evidence to support the use of progesterone cream as adequate to prevent the endometrial hyperplasia related to estrogen therapy.
  • An association between post-menopausal hormone replacement and improvement in depressive symptoms has not been shown.
  • There is not evidence to support an association between post-menopausal hormone replacement and prevention of Alzheimer’s disease.
  • The touted improved safety and better efficacy of “bio-identical” hormonal products over standard hormone replacement therapy is very suspect.
While the term “bio-identical” may refer to standard brand name and tested hormonal products, such as 17B-estradiol or micronized progesterone, the terminology more commonly refers to custom compounded products that have not been tested and are not approved. Furthermore, the dosing of such products on the basis on salivary testing has not been shown to be either reliable or accurate.

In summary, the most current expert advice is that the lowest dose of HRT required should be used to treat symptoms of menopause if needed and continued for ideally less than 5 years. The doses of HRT on the market currently are lower than those studied in the WHI and may be safer, though this still remains unproven. Transdermal therapy may be preferable over oral therapy. There is no standard procedure for the discontinuation of HRT.

The assessment of a patient's personal risk profile and preferences and clinical flexibility are key to treating postmenopausal women with HRT. We all take risks in life. Some women feel better on perpetual hormone replacement therapy and that’s ok, but I personally feel more confident prescribing formulations that are better understood.

1 comment:

  1. As i evaluate the pros and cons of Postmenopausal Hormone Replacement Therapy, My take is to go against it. Though we know that it will alleviate the discomforts of one is experiencing during menopausal stage but on the other side, we dont know the possible side effects of this therapy.