Update on Hormone Replacement: Sorting Out the Options for Preventing Coronary Artery Disease and Osteoporosis

, Ohio State University

In This Article

Hormone Replacement Therapy Goals and Regimens

Long-term estrogen replacement is an effective therapy for osteoporosis prophylaxis and treatment. The decision-making processes regarding HRT use are summarized in Figures 2 and 3.[15] However, treatment plans must be tailored to the individual woman. The goals of HRT are to use the minimum effective replacement dosage to suppress vasomotor symptoms, treat urogenital atrophy, prevent bone loss, and potentially reduce the risk of cardiac disease.[16]

Figure 2. Hormone replacement therapy (HRT) in a menopausal woman who has had hysterectomy calls for prescribing estrogen replacement therapy (ERT) not only to relieve menopausal symptoms, but to protect against bone and cardiovascular problems associated with estrogen depletion.
Figure 3. In a menopausal women with a uterus, progestin-estrogen replacement therapy (PERT) with cyclic or continuous progestin is needed to prevent endometrial hyperplasia associated with estrogen therapy.

Oral Estrogens. The minimal effective dose for most menopausal women is generally equivalent to 0.625mg of conjugated equine estrogens (Table I). Since the majority of studies showing cardiovascular benefit have used conjugated equine estrogens (Premarin), that form of estrogen is often prescribed to reduce the risk of cardiovascular disease. Esterified estrogens (Estratab, Menest), which are principally a combination of estrone and equilin sulfate, are not biochemical equivalents of conjugated equine estrogens, but may be cost-effective alternatives for the treatment of vasomotor symptoms.

Micronized 17-B estradiol (Estrace) is the principal estrogen secreted by the pre-menopausal ovary. When given orally, micronized 17-B estradiol is rapidly absorbed and is conjugated and metabolized within the liver to estrone. This form of estrogen increases sex-hormone-binding globulin levels, which may make it particularly advantageous for women with androgen excess involving skin- and hair-related postmenopausal problems. The short half-life of oral, micronized 17-B estradiol however, necessitates splitting the total dosage into a bid regimen.

Purified estropipates (Ogen, Ortho-Est), because they contain weak estrone (E1) without any stronger equine estrogens, are physiologically weaker than conjugated or esterified estrogens of comparable milligram dosage. For adequate osteoporosis prophylaxis, a high dose of estrone and/or additional calcium supplementation may be needed. Weaker estrogens may be advantageous in women prone to mastalgia, however. For women without vasomotor symptoms who cannot tolerate higher dosages of estrogen because of breast tenderness or fluid retention, the lowest dose of purified estropipates (0.625mg) is a scored tablet that can be broken in half. Conjugated equine estrogens (0.3 mg) and micronized 17-B estradiol (0.5mg) also have very-low-dose ERT alternatives.

Transdermal patches. The standard minimum oral estrogen doses of conjugated equine estrogens 0.625mg and micronized 17-B estradiol 1mg are comparable in strength to the 0.05mg transdermal 17-B estradiol patch (Estraderm), which must be applied to the skin on the abdomen every 3-1/2 days (Table II). This reservoir patch, which contains only an adhesive and transdermal 17-B estradiol, may cause skin irritation in some patients. Transdermal estradiol avoids enterohepatic metabolism and the consequent potential effects on hepatic coagulation proteins. A remote history of venous thrombosis is not a contraindication for ERT, but high doses of estrogen should be avoided. To minimize risk of vascular clotting problems, the low-dose transdermal estradiol reservoir patch may be preferred to oral preparations in women with a history of thromboembolism.

More recently, transdermal estradiol matrix patches have been introduced. The matrix patches appear to offer better adhesion with less skin reaction than reservoir patches. The first was Climara, which is available in 2 strengths (0.05mg and 0.10mg) and only needs to be changed once weekly. The most recent is Vivelle, which has 4 dosage strengths (0.0375mg, 0.05mg, 0. 075mg, and 0.10mg) but must be changed twice per week like the reservoir patch.


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