Bone Effects. Estrogen has multiple actions that influence bone health and overall women's health. Actions that influence bone density include regulation of calcium absorption and excretion by directly or indirectly modulating PTH, calcitonin, activated vitamin D, and intestinal calcium receptors, and regulation of metabolic bone activity by exerting effects on estrogen receptors located on osteoclasts and osteoblasts. Estrogen produces a transient uncoupling of bone remodeling, slowing resorption and allowing formation to continue until a new equilibrium is established.



Other Effects.Consensus regarding potential extraskeletal benefits such as cardiovascular protection, improvement of vasomotor symptoms, and reduction in overall mortality is available elsewhere, and discussed. Controversy regarding breast cancer risk and other side effects often dissuades women from beginning HRT. Both potential benefits and risks of HRT need to be discussed prior to initiation of therapy in postmenopausal women.

Therapeutic Effects.ERT or HRT (estrogen with progestin for women with an intact uterus) is one of two first-line therapies for the prevention and treatment of osteoporosis. The U.S. Preventive Services Task Force recommends that all postmenopausal women receive counseling about HRT, regardless of age. The estrogen effect on bone remodeling appears to operate at all ages and is independent of the course or time since onset of menopause. Recent data suggest that ERT be continued into late life for the maintenance of high bone density. Past estrogen use does not provide long-term benefit for preservation of bone density. However, the optimal age for initiating ERT is controversial because similar bone density benefit was observed in women who began ERT after age 60.

Dosing Regimens. The suggested doses for ERT for osteoporosis prevention are presented. The majority of epidemiologic data about the safety and efficacy of estrogens relate to oral use; conjugated equine estrogens (Premarin) 0.625 mg is the most common dose studied. However, estrogens reduce bone turnover when administered transdermally, percutaneously, subcutaneously, and intravaginally, provided doses are sufficient, Vaginal estrogen creams are not routinely used for systemic purposes due to very short half-lives and minimal effects in the systemic circulation or on the endometrium unless given frequently and for a long period of time. Vaginal estradiol tablets and vaginal rings are also available, but use is limited to treatment of genitourinary symptoms because these dosage forms do not provide protection against osteoporosis or ischemic heart disease.

Continuous HRT (estrogens and progesterones dosed daily) appears to be similar to cyclic HRT in preserving bone mass at cortical and trabecular bone sites. In addition, continuous therapy resulted in 93 percent compliance after 1 year of treatment compared with 66 percent compliance in women on traditional cyclic therapy. Cyclic therapy is preferred during the first 5 years of menopause because a more physiologic hormone delivery is provided and less breakthrough bleeding occurs.

Side Effects and Contraindications. Common adverse effects for HRT include vaginal spotting and bleeding; breast tenderness and breast enlargement, especially in older women; and pedal edema. Compliance with ERT/HRT is an important issue to address. The two most common reasons women discontinue usage are vaginal bleeding and breast tenderness. Women need to be educated about vaginal bleeding and its expected onset, frequency, and duration. Dosage manipulations may be required to control and eliminate vaginal bleeding. If continuous therapy is used and amenorrhea does not develop after 6-12 months, following a workup to rule out abnormal causes of bleeding is suggested; predictable bleeding patterns with cyclic therapy may be preferred for these women. Breast tenderness may decrease with time. Other management options are described. The benefits versus risks, including adverse reactions, must be continually assessed.