MANAGEMENT OF MENOPAUSE
The changes of menopause result from declining 17-β estradiol production by the ovarian follicles. 17-β estradiol and its metabolic by-products, estrone and estriol, are used in hormone therapy, the objective of which is to diminish the signs and symptoms of menopause. Several differentestrogen preparations are available through various routes of administration, including oral medications, transdermal prepa-rations, and topical preparations. When administered orally,17-β estradiol is oxidized in the enterohepatic circulation to estrone. 17-β estradiol remains unaltered when it is admin-istered transdermally, transbucally, transvaginally, intra-venously, or intramuscularly. Unfortunately, intramuscular estradiol administration results in unpredictable fluctua-tions in plasma concentration. When estradiol is adminis-tered across the vaginal epithelium, absorption is poorly controlled, and pharmacologic plasma concentrations of estradiol can result. Transdermal administration of estra-diol results in steady, sustained estrogen blood levels and may be a preferable alternative to oral dosing for many patients.
The administration of continuous unopposed estrogens can result in endometrial hyperplasia and an increased risk of endo-metrial adenocarcinoma. Therefore, it is essential to administer a progestin in conjunction with estrogens in women who have not undergone hysterectomy. Progestins may include any varietyof synthetics, such as medroxyprogesterone acetate and norethindrone or micronized progesterone. To achieve this protective effect, the progestin chosen may be given continuously in low doses or sequentially in higher doses. Sequential dosing is usually for 10 or 12 days each calendar month. Progestins may be associated with unacceptable side effects, such as affective symptoms and weight gain. If estrogen is administered alone because of unacceptable side effects of progestins, then it is imperative to counsel the patient about the need for yearly endometrial biopsy.
There are two principal regimens for hormone therapy. Continuous estrogen replacement with cyclic progestin administration results in excellent resolution of symptoms and cyclic withdrawal bleeding from the endometrium. One of the difficulties of this method of therapy is that many postmenopausal women do not want to continue having menstrual cycles. As a result, many physicians and patients choose to avoid the problem of cyclic withdrawal bleeding by the daily administration of both an estrogen and a low-dose progestin.
There are a variety of estrogen preparations available. Most perimenopausal and menopausal women respond to one of these preparations, all of which ameliorate acute menopause symptoms and relieve vaginal atrophy. The administration of progestins for 10 to 12 days each month converts the proliferative endometrium into a secretory endometrium, brings about endometrial sloughing, and prevents endometrial hyperplasia or cellular atypia. Contin-uous progestin therapy may be used to produce endome-trial atrophy.
Numerous preparations combining estrogen and pro-gestins are available in both oral and transdermal formu-lation. The most widely used contain a combination of conjugated equine estrogens and medroxyprogesterone acetate in one tablet. Newer preparations include a combi-nation of micronized estradiol and norethynodrel acetate or ethinyl estradiol and norethindrone acetate. Transdermal preparations include a combination of micronized estradiol and norethindrone acetate. Low-dose oral contraceptives mayalso be used to relieve the vasomotor symptoms of menopause.