Hormone Replacement Therapy

Hormone replacement therapy (HRT) refers to the practice of replacing normally-produced hormones with similar or identical hormones from other sources. The hormone(s) in question may be missing because of a disease process such as type 1 diabetes, where the missing hormone (insulin) is injected to sustain life, or the hormone to be replaced may be missing because of a surgical intervention, such as thyroidectomy (removal of the thyroid gland) resulting in the need for thyroid hormone replacement. Many other hormones can be synthetically prepared and used as needed in medical treatments, and the hormone to be replaced need not be completely absent.

This page discusses HRT in the context of part of a woman's normal aging process, menopause, that results in low levels of estrogen and progesterone (called progestin in its synthetic form). Many of the troublesome symptoms of menopause can be significantly altered by HRT. The great number of women on HRT has allowed large epidemiologic studies to estimate the risks and benefits, which help individual women and their doctors make informed choices about the therapy.

Other Names

• Estrogen replacement therapy
• ERT

Description

Many different hormones are involved in regulation of a woman's menstrual cycle and reproductive health. Estrogen, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) are among the most important. Menopause or the climacteric results when estrogen production by the ovaries declines gradually over several years. The woman no longer ovulates and menstrual cycles eventually stop. A woman is considered to be post-menopausal when she has not had a menstrual period for 1 year.

The mean age of menopause in the United States is between 51 and 52 years. Most women have several years (median 4 years) of irregular menstruation preceding actual menopause. The median age of onset of the perimenopause is 47.5 years. The age at which perimenopause begins and menopause occurs is genetically determined. It is unrelated to the number of ovulations that occur during a woman's lifetime.

For some women menstrual periods stop abruptly and that is their only menopausal symptom. However, this is true for only about 10% of women. For most women, menopausal symptoms range from mild to severe. Symptoms may begin during the perimenopause and can continue for years. Some women experience symptoms such as menstrual irregularities, hot flashes, mood swings and vaginal dryness as early as age 35. For the majority of women these symptoms improve with time, but for some women they are lifelong.

For women who are symptomatic, HRT can be helpful. Taking estrogen replacement by pills or by patches will lessen the severity of hot flashes, vaginal dryness and night sweats that characterize menopause. If the woman has an intact uterus, she will need to take progesterone in addition to the estrogen to help protect the uterine lining from getting too thick. If a woman's uterine lining is exposed to estrogen without progesterone to balance it, the lining (also called endometrium) can become cancerous over time. If the woman has had a hysterectomy (removal of the uterus), then she will only need to replace estrogen.

Why Hormone Replacement Therapy Is Done

Generally, health care providers prescribe HRT for three groups of women:

• Women going through peri-menopause and/or menopause — The natural levels of estrogen and progesterone drop during the peri-menopause and continue to decline until menopause is reached. This drop in hormone levels can lead to symptoms such as hot flashes, night sweats, vaginal dryness, menstrual irregularities, mood swings and sleep disturbances. HRT may be used to control these symptoms.

• Women with certain health conditions — In some cases, women’s bodies don’t make normal levels of the hormones because of medical problems.

• Premature ovarian failure is when a woman's menstrual periods stop before the age of 40. These conditions can be caused by genetic abnormalities. Turner's Syndrome is an example of such a condition. For these women, HRT replaces the hormones that their bodies prematurely stop making. For some women, this reduction in hormone levels occurs at very early ages.

• Surgical Menopause- A third category of women includes those who have had their ovaries removed surgically because of problems with their ovaries or uterus. In some cases the ovaries and the hormones they produce must be removed at a young age. The transition to menopause is abrupt rather than gradual for these women and therefore they have more severe symptoms. Gynecologists recommend replacing estrogen in women going through surgical menopause.

What Is Hormone Replacement Therapy

Hormone replacement therapy is just that; hormones are used to replace the ones that are no longer made by the ovaries at menopause. Prior to menopause, the ovaries produce estrogen and progesterone which regulates ovulation and menstrual periods as well as conception. After menopause, hormones that are replaced include either estrogen, or progesterone, or a combination of the two hormones.

For women who have an intact uterus (eg. it has not been surgically removed) a combination of estrogen and progesterone is usually prescribed. Taking estrogen alone unopposed estrogen increases the risk of cancer of the lining of the uterus (endometrium). Adding progesterone prevents the uterine lining (endometrium) from thickening and reduces the uterine cancer risk to the level of using no hormones. Progesterone can be given in moderate doses for 10-14 days per month, or in lower dosages daily. The progesterone protects the uterine lining from becoming cancerous.

Benefits

Women whose bodies have stopped making estrogen prematurely or never made enough estrogen often take HRT to reduce symptoms and maintain overall health. Low estrogen levels in young women put these women at risk for osteoporosis and heart disease. HRT helps maintain bone health and reduce the risk of heart disease. In these cases, HRT is actually replacing hormones that the women’s bodies should be making hormones that they need for their overall health. HRT taken by women with certain health conditions is different than that taken my post-menopausal women. The risks associated with post-menopausal HRT do not normally apply to pre-menopausal women taking HRT, in fact their risks are statistically lower than they would be if these women's bodies made hormones naturally.

For women who are perimenopausal, one of the biggest benefits of hormone replacement therapy is control of irregular menstrual cycles. HRT can be prescribed to regulate or eliminate menstrual periods which are often very unpredictable at this time of life. Other benefits include relief of symptoms such as hot flashes, mood swings, night sweats, insomnia, and others which may severely affect a woman's quality of life. Low doses of hormones are often very effective and are often needed for only short periods of time.

Risks

The risks of HRT differ depending on the health status of the woman taking it, and on the type of HRT.

The NIH conducted the Women's Health Initiative (WHI) trial to learn about the risks and benefits of continuous estrogen+progestin HRT for post-menopausal women.

• In one arm of this trial and as described in subsequent reviews, researchers found that healthy post-menopausal women who took the therapy were at increased risk of invasive breast cancer ^[1], coronary artery disease^[2], stroke^[3], and blood clots^[4]. There were also benefits of estrogen plus progestin, including fewer cases of hip fractures^[5] and colon cancer.^[6]
• Because the risks of HRT for healthy post-menopausal women in this trial was greater than the benefit, the researchers stopped the trial.
• In light of the findings, the U.S. Food and Drug Administration noted that even though HRT effectively lessened some symptoms in healthy menopausal women, it carried serious risks. It is important for a woman to discuss the potential benefits and risks of HRT with a health care provider. The FDA recommends that HRT for post-menopausal women be at the lowest doses for the shortest amount of time to reach treatment goals.

Alternative and Complementary Medicines for Menopausal Symtoms

Some women consider alternatives to menopausal hormone therapy (traditional HRT) to ease menopausal symptoms. Some alternative therapies may have side effects or may make another drug that the patient is already taking not work as well. In addition, recent studies have shown that some herbal supplements contain unsafe levels of lead.^[7]

Common alternative therapies for menopause:

• Soy and other foods containing phytoestrogens, which are estrogen-like substances made by plants. Other sources of phytoestrogens include herbs such as black cohosh, wild yam, dong quai, and valerian root.
• Bioidentical hormone therapy

There are two main types of Bioidentical hormones:

1. Those that are FDA-approved and commercially available with a prescription.
2. Those that are mixed on an individual basis for women in compounding pharmacies. These are not FDA-approved and have not been studied in long term scientific studies.

References

1. ↑ Coombs NJ, Taylor R, Wilcken N, Boyages J. Hormone replacement therapy and breast cancer: estimate of risk. BMJ. 2005 Aug 6;331(7512):347-9. Citation | Full text | PDF
2. ↑ Humphrey LL, Chan BK, Sox HC. Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease. Ann Intern Med. 2002 Aug 20;137(4):273-84. Abstract | Full Text | PDF
3. ↑ Bath PM, Gray LJ. Association between hormone replacement therapy and subsequent stroke: a meta-analysis. BMJ. 2005 Feb 12;330(7487):342. Abstract | Full Text | PDF
4. ↑ Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008 May 31;336(7655):1227-31. Abstract | Full Text | PDF
5. ↑ Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA. 2001 Jun 13;285(22):2891-7. Abstract | Full Text | PDF
6. ↑ U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med. 2002 Nov 19;137(10):834-9. Summary for Patients | Abstract | Full Text | PDF
7. ↑ Mazzanti G, Battinelli L, Daniele C, et al. Purity control of some Chinese crude herbal drugs marketed in Italy. Food Chem Toxicol. 2008 Jun 11. Abstract

Other Resources

• For more information about the WHI and its findings on post-menopausal HRT, visit NIH Web Page on the Women's Health Initiative.

• The National Institute on Aging: Hormones and Menopause

• (National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): Osteoporosis

• FDA: Menopause

• The North American Menopause Society:
  • Understanding Menopause
  • Menopause Basics (FAQs)