Hormone replacement therapy

From Academic Kids

This article is about the treatment with sex steroids. For hormone replacement therapy in general, and for other instances in which hormones might be prescribed, see hormone therapy.

Hormone replacement therapy (HRT) is a system of medical treatment for postmenopausal women, based on the assumption that it may prevent health problems caused by diminished circulating estrogen hormones. The treatment involves a series of drugs designed to artificially boost hormone levels. Estrogens and progestagens are the two main types of hormones involved.

HRT is also used by transgendered or transsexual people to aid them in attaining the secondary sex characteristics of their desired sex. See Hormone replacement therapy (trans). It is also given to some intersex people (depending on the precise intersex condition), either starting in childhood to confirm the gender they were assigned, or later, if this gender assigment has proven to be incorrect.

HRT provides low dosages of an estrogen and a progestagen. In women who have had a hysterectomy only an estrogen is given, unopposed estrogen therapy. HRT treatment is by tablets taken either cyclically (estrogen daily and progestagen from around two weeks every month; sequentially combined HRT or scHRT) or continuously (constant dosage of both types of hormones; continuous combined HRT or ccHRT). Sometimes also an androgen is added to treat reduced sexual desire (libido) after menopause.

It is seen as either a short-term relief (often one or two years, usually less than five) from menopausal symptoms (hot flashes, irregular menstruation, fat redistribution etc.) or as a longer term treatment to reduce the risk of osteopenia leading to osteoporosis.

There are certain potential risks associated with HRT. Oral estrogen intake can exacerbate existing liver or gallbladder problems and cause blood clots. Estrogens can also effect blood triglyceride levels and so may increase the risk of cardiovascular problems. Long term use of HRT may also increase the risk of breast cancer. Unopposed estrogen therapy in women with a uterus may also increase the risk of uterine cancers.

Due to the potential problems of HRT a number of alternative therapies have been used. A mix of different drugs to control symptoms is one approach, as are certain changes to the diet and regular exercise. To combat the risk to bones dietary changes to increase calcium uptake, exercise, and drugs such as biphosphates, selective estrogen receptor modulators or calcitonin have been tried. The use of supplements containing the naturally occurring hormones estradiol, progesterone, estriol, and testosterone with an emphasis on topical administration of the hormones is often called bioidentical hormone replacement therapy (BHRT)[1] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15167316). BHRT has gotten much discussion since being advocated by celebrities such as Suzanne Somers, Robin Strasser, Patti LaBelle, and Valerie Harper.

Although HRT was once widely thought to promote cadiovascular health in women, on February 4, 2004, the American Heart Association released guidelines stating that HRT should not be considered as an agent to increase heart health or to decrease the chances of cardiovascular disease.

Results of the WHI hormone replacement therapy studies

Much of the controversy regarding hormone replacement therapy (HRT) result from a study by the Women's Health Initiative, which came out in 2002 [2] (http://jama.ama-assn.org/cgi/content/abstract/288/3/321%20). It followed 16,608 women, aged 50 to 79 (average age = 63 at study intake), for 5.2 years who were either on combined oestrogen and progestogen HRT (8506 women) or a placebo (8102 women). It found that the measured risks of HRT outweighed the measured benefits in this study (see the table, below).

Adverse event

Relative risk
(95% CI)

Change in number of events
per 10,000 women in one year

Breast cancer

1.26 (1.00-1.59)

8 more

Heart disease

1.29 (1.02-1.63)

7 more

Stroke

1.41 (1.07-1.85)

8 more

Pulmonary embolism

2.13 (1.39-3.25)

8 more

Colorectal cancer

0.63 (0.43-0.92)

6 fewer

Hip fracture

0.66 (0.45-0.98)

5 fewer

It is not clear to what extent the results of the Estrogen-plus-Progestin study (above) should be applied to women who begin HRT at a young age. For the women age 50-59 in this study, there was an observed trend towards a reduced risk of cardiovascular disease (relative risk = 0.56, 95% CI 0.30-1.03) and a statistically significant increase in blood clotting was not observed (relative risk for stroke = 1.08, 95% CI 0.57-2.04). It is not clear if the results of this study are relevant to other forms of estrogen replacement therapy such as topically administered estradiol. Results from other studies suggest that when estrogens are administered orally, liver function is altered and the risk of blood clots is increased [3] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12927428). The results of the WHI Estrogen Alone clinical trial suggest that the synthetic progestin used in the Estrogen-plus-Progestin study was the cause of the increased risk of breast cancer. In the Estrogen Alone clinical trial [4] (http://jama.ama-assn.org/cgi/content/full/291/14/1701) there was an observed trend towards a reduced risk of breast cancer (relative risk = 0.77, 95% CI 0.59-1.01).

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