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Hormone Replacement Therapy

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Title:   Hormone Replacement Therapy


Hormone replacement therapy (HRT) generally means medications containing hormones to replace the ones that body no longer or less produce in patients. This is due to the primary failure of development of the organ (e.g., the ovaries, or testis), premature menopause, castration, or menopause. Therefore, the hormones to be replaced could be female hormones (estrogens and progestin), male hormones (testosterone) or other hormones (thyroxin, insulin, growth hormone etc.).


Menopausal Hormone Therapy (MHT)

HRT containing female hormones usually called Menopausal Hormone Therapy (MHT) used to be a standard treatment for women with menopause symptoms (hot flushes, inappropriate sweating, urogenital atrophy).

Standard MHT during natural (non surgical) menopause take estrogens alone or combine with progestin. Conjugated estrogens and medroxyprogesterone acetate (MPA) have been the most common agents for post-menopausal use, although estradiol, estrone, and estriol have been used as estrogens, and norethindrone, norgestimate, levonorgestrel, norethisterone, and progesterone also have been widely used. MHT could be administered orally or locally. Regardless of the specific agent or regimen, MHT with estrogens should use the lowest dose and the shortest duration necessary to achieve therapeutic goal.

The Benefit of MHT

The established benefit of estrogen therapy in postmenopausal women include amelioration of vasomotor symptoms and prevention of osteoporosis, vaginal dryness, and urogenital atrophy

Vasomotor symptoms associated with the decline in ovarian function. The characteristic hot flushes may alternate with chilly sensations, inappropriate sweating, and paresthesias. Treatment with estrogen is specific and is the most efficacious pharmacotherapy for this symptoms

Osteoporosis is a disorder of skeleton associated with the loss of bone mass. The primary mechanism by which estrogens act is to decrease bone resorption; so estrogens are more effective at preventing rather than restoring bone mass. Estrogens are more effective if treatment is initiated before significant bone loss occurs, and their maximal beneficial effects require continuous use; bone loss resumes when treatment is discontinued.

Vaginal dryness and Urogenital atrophy . Loss of tissue lining the vagina or bladder leads to variety of symptoms in postmenopausal women. These include dryness and itching of the vagina, dyspareunia, swelling of tissues in the genital region, pain during urination. Estrogens administered locally or orally may relief the vulvar and vaginal atrophy.

Cardiovascular disease. Epidemiological studies consistently showed an association between estrogen use and reduced cardiovascular disease in postmenopausal women. Furthermore, estrogens produce a favorable lipoprotein profile, promote vasodilatation, inhibit the response to vascular injury, and reduce atherosclerosis. Studies such these led to widespread use of estrogens for preventing cardiovascular disease in menopausal women.

MHT may help alleviate or lessen some of those menopausal symptoms by direct actions (e.g., improvement of vasomotor symptoms) or secondary effects resulting in an improved feeling of well being. Conjugated estrogen in combination with progestin also shown a small protection against colon cancer.


The Risk of MHT

In the larger clinical trial from the Women’s Health Initiative (WHI) project, estrogen plus progestin replacement therapy showing no cardiovascular benefit in perimenopausal or older post menopausal patients. In fact, there maybe a small increase in cardiovascular problem as well as breast cancer.  .

Several randomized, prospective studies unexpectedly indicated that the incidence of heart disease and stroke in older post menopausal women treated with conjugated estrogens and progestin was initially increased, although the trend reversed with time. While it is not clear if similar results would occur with different drugs/doses or in different patient population.


Who should consider Hormone Therapy?

Despite the health risk, estrogen is still the gold standard for treating menopausal symptoms. The absolute risk of an individual woman taking hormone therapy is quite low enough to be acceptable depending on their symptoms.

The benefits of short-term hormone therapy may over weigh the risk, if:

  1. Experience moderate to severe hot flushes or other menopausal symptoms
  2. Have loss bone mass and either aren’t able to tolerate or aren’t benefiting from other treatments
  3. Stopped having periods before age 40 (premature menopause) or lost ovaries before age 40 (premature ovarian failure); these women have:
    • a lower risk oh breast cancer
    • a higher risk of osteoporosis
    • a higher risk of coronary heart disease (CHD).


Hormone therapy appears to reduce the risk of osteoporosis and CHD when started soon after menopause in young women. For women who reach menopause prematurely, the protection benefit of hormone therapy may over weigh the risk. However, estrogen (alone or in combination with progestin) should not be used for the treatment or prevention of cardiovascular disease.



1.      David S. Loose and George M. Stancel. Estrogens and Progestins. In: Brunton LL. Lazo JS. and Parker KL, editors. Goodman & Gilman’s The pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill Medical Publishing Division. 2006: 1553-1554.

2.      George P. Chousos. The Gonadal Hormones & Inhibitors. In: Katzung BG. Masters SB. and  Trevor AJ, editors. Basic & Clinical Pharmacology. 11th ed. Boston: McGraw-Hill Medical Publishing Division. 2007: 658-660.