Benefits of Postmenopausal Hormone Therapy

i) Symptoms of menopause:

estrogen therapy is very effective in reducing vasomotor (eg hot flushes)and genitourinary symptoms.

For genitourinary symptoms (such as vaginal atrophy), vaginal estrogen is as good as transdermal or oral estrogen.

Vasomotor symptoms may be reduced by venlafaxine, 75 to 150mg/d, clonidine 0.1 to 0.2 mg/d or vitamin E (400 to 800 IU/d). The consumption of soy-based products or other phytoestrogens  may also reduce vasomotor symptoms. Generally these are less effective than estrogen therapy.

ii)Osteoporosis:

estrogen reduces bone turnover and resorption.  This slows the aging-related bone loss in postmenopausal women.It is well established that postmenopausal estrogen therapy (with or without progestin), increases bone mineral density at the spine (by 4 to 6%) and hip (by 2 to 3 %). This increase is also maintained during treatment.

Reduced incidence of fractures

There is a 50 to 80% lower risk of vertebral fracture among current estrogen users. There is also a 30% reduction in the risk of hip, wrist and other peripheral fractures. However once the estrogens are discontinued the protection is diminished.

Bisphosphonates (eg alendronate, 10mg/d or 70mg once a week,residronate 5mg/d or 35mg once a week) and selective estrogen receptor modulator (eg raloxifene 60mg/d) increases bone mass and density (randomized trials) and reduces fracture rates.

The risk of osteoporosis related fractures may be reduced by increasing physical activity, taking adequate calcium (1000 to 1500mg/d in two to three divided doses) and vitamin D (400 to 800 IU/d).

Risks of Postmenopausal Hormone Therapy

i) Endometrial cancer:

In short term users of unopposed estrogen (1-5 years) there is a three fold increase risk of endometrial cancer. In long term users (10 years or greater) there is nearly a 10 fold increased risk of endometrial cancer.

In the postmenopausal estrogen/progestin intervention trial (PEPI) up to 24% of women developed atypical endometrial hyperplasia (a premalignant lesion) after being assigned to take unopposed estrogen for 3 years. Only 1% of women assigned to placebo developed endometrial hyperplasia. Progestin eliminates these risks by opposing the effects of estrogen in the endometrium.

ii) Venous thromboembolism:

According to a recent meta-analysis of 12 studies. There was a two-fold increase risk of venous thromboembolism in postmenopausal women.

iii) Breast cancer:

There is an increased risk of breast cancer among estrogen users. The risk of breast cancer is directly related to the duration of of use. Long term use (5 years or greater) was associated with a 35% increased risk of breast cancer (meta-analysis of 51 case-controled and cohort studies). Unfortunately unlike in endometrial cancer combined estrogen-progestin regimens increase breast cancer risk more than estrogen alone.

References:

Pages 2209 to 2212.Chapter 327. The menopause transition and postmenopausal hormone therapy.Harrisons Principles of Internal Medicine. Volume II.16th edition. Kasper,Braunwald,Fauci,Hauser,Longo and Jameson.

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