Estrogens from Reproductive Life to Menopause From puberty to menopause, the ovaries produce estrogen (estradiol), and when ovulation occurs, progesterone is added. The ovaries also produce the male hormones testosterone and androstenedione. Estrogen and progesterone act on their target organs, so called because they contain specific receptors or receiving areas where these hormones can enter the cells and produce the required effect. The target organs for estrogen and progesterone are the breasts, vulva, vagina, uterus, urethra, bladder, skin, and parts of the brain that control mood, sleep (insomnia), and temperature (hot flashes).
After menopause, the ovaries secrete very little estradiol, so the total amount of estrogen in the body drops to only a fraction of that produced during reproductive life. As a result, an alternative though small source of estrogen becomes significant. Male hormones continue to be produced by the adrenal gland—and, important, also by the ovaries—for about five years after menopause (the increased facial hair that women report in the early postmenopausal years is the result of the male hormones that continue to be secreted). These male hormones are carried to the skin, liver, body fat, and brain, where they are converted to a weak but effective estrogen, estrone. Body fat is a particularly important site of estrone production; it has long been recognized that women with more body fat have higher circulating estrone levels.
Why Is Estrogen Important? The degree to which estrogen affects the tissues becomes evident after menopause, when levels of estrogen drop. Following menopause, the deficiency in estrogen causes obvious symptoms such as hot flashes, insomnia, vaginal dryness, increased urinary frequency, increased incidence of bladder and vaginal infections, and in the long-term osteoporosis and a predisposition to arteriosclerosis. Hormonal replacement therapy (HRT) provides symptomatic relief whenever it is begun and is particularly important when the production of estrogen stops prematurely (before the age of forty)* because the long-term consequences (bone loss and cardiovascular problems) are often even more significant.
What Are Menopause and Premature Ovarian Failure? Menopause means that the periods (“menses”) have stopped (“paused”). Menopause occurs naturally around age fifty. However, radiation, chemotherapy, or surgical removal of the ovaries before menopause will result in ovarian hormone deficiency even earlier. In younger women who have experienced premature ovarian failure as a result of chemotherapy or radiation therapy, the ovaries may later begin to function again. Although we are unable to predict whether this will occur, factors that appear to play a role are age and type and amount of chemotherapy or radiation. Until ovarian function resumes, these women should be on hormonal replacement therapy and, if pregnancy is not desired, also on some form of contraception.
Hormonal therapy prescribed after menopause is often called estrogen therapy (ET) or hormone replacement therapy (HRT), which usually means estrogen with progestin therapy.
HRT Medications There are many possibilities for hormonal replacement therapy. Nonsmoking reproductive-aged women with premature ovarian failure (POF) are often best treated with birth control pills (oral contraceptives), which contain adequate amounts of both estrogen and progestin. The advantages of this approach are that the higher dose of hormones in birth control pills is what is often needed to control estrogen-deficiency symptoms in younger women, and that at the same time, it provides contraceptive protection should the ovaries begin to function again.
When vaginal or urinary symptoms persist despite systemic hormonal therapy, local hormonal therapy may be added. This may be in the form of an estrogen vaginal cream like Premarin or Ortho-Dienestrol (dienestrol; no longer available in Canada), estradiol vaginal tablets (Vagifem), or an estradiol vaginal ring (Estring).
Standard hormonal therapy consists of estrogen preparations, which include oral estrogens such as conjugated estrogen tablets (Premarin), estrone (Ogen), and estradiol (Estrace); an estradiol gel (EstroGel); and a transdermal estradiol patch (Estradot, Estraderm, or Climara). Women who have not had a hysterectomy need to add a progestin—either medroxyprogesterone acetate (Provera), norethindrone (Norlutate), or progesterone (Prometrium). Estrogen-progestin combinations may be used together, continuously (nonstop) or cyclically (i.e., estrogen alone for about two weeks, then estrogen with the addition of a progestin for an additional ten to fifteen days). Two products that contain a combination of both estrogen and progestin are available: CombiPatch, a transdermal estradiol-norethindrone patch, and FemHRT, an oral pill that contains ethinyl estradiol and norethindrone.
Another possibility is an implant under the skin (subdermal implant) of nomestrol acetate (Uniplant), which needs to be replaced every six months. This preparation currently is not available for use in Canada. For many years, a popular form of postmenopausal replacement therapy has been an injection of Duratestin, which is a combination of estradiol and testosterone that is given intramuscularly every six weeks. This preparation not only treats estrogen-deficiency symptoms, but also may improve libido as a result of the testosterone in the mixture. Occasionally, a small dose of testosterone is prescribed alone, specifically to treat problems of decreased libido. Oral tablets of Andriol (testosterone undecanoate) may be used two to three times per week and are available on prescription in Canada. Testosterone creams and gels in doses appropriate for women are not commercially available but can be compounded by some pharmacies for topical transdermal applications. A testosterone patch (Intrinsa) has been widely tested in North America and found to be effective in the treatment of women distressed about their problem of low libido. The testosterone patch is currently under review by Health Canada, and it is hoped that they will approve the use of this product in the near future.
Treatment Routines Estrogen with or without a progestin may be given cyclically (resulting in “menstrual periods”) or in a continuous combined nonstop regimen (no “menstrual periods”). A common routine using both estrogen and progestin is to give estrogen alone for fourteen to fifteen days, then add progestin (such as medroxyprogesterone acetate [Provera]) for seven to fourteen days. Both hormones are then stopped, and a period follows in one or two days. The cycle is repeated monthly.
Similarly, if continuous estrogen is given and progestin is added only for twelve to fourteen days, a period is expected one or two days after the progestin is stopped. This routine is commonly used with transdermal preparations.
For women who do not wish to have a period but want and need HRT, a combined routine of estrogen and progestin is given continuously. After a short adjustment period (approximately six months) during which some vaginal bleeding may occur, most women enjoy all the benefits of HRT, including relief of hot flashes, insomnia, and vaginal and urinary symptoms.
Effects of HRT HRT has numerous normal effects, not all of which are welcomed by women. These effects, addressed below, are the result of estrogen’s effects on the target organs and tissues. Obvious early benefits include a reduction in hot flashes and night sweats and more restful sleep. Some women also report a greater sense of well-being.
After a few months’ treatment, women may notice other beneficial effects. The vagina and cervix can be expected to become healthier and more moist with increased vaginal secretion and better lubrication during intercourse. Many women also report increased sexual awareness and enhanced sexual response after starting hormone replacement therapy. In addition, fewer bladder and vaginal infections occur.
However, there may be some normal but undesirable effects as well, including increased sensitivity and sometimes tenderness of the breasts, increased vaginal discharge, and the return of vaginal bleeding, or “menstruation.”
Is Hormonal Replacement Therapy (HRT) for You? Whether or not systemic HRT is appropriate or likely to prove beneficial for you can best be decided by your doctor. Talk to him or her about the possibility of this treatment. You may be an ideal candidate. This is particularly likely if your periods have stopped and menopause has occurred in your early forties or before. On the other hand, you may want or need to manage your symptoms without hormones.
Management of Menopausal Symptoms Without Hormonal Replacement Standard estrogen therapy may not be safe or appropriate for some; thus, it is heartening that considerable research has been directed to finding other, nonhormonal and nonmedical approaches that can improve sexual functioning and menopausal symptoms after breast cancer.
These include giving patients access to educational pamphlets discussing menopause, estrogen replacement therapy, urinary incontinence, tamoxifen (Nolvadex), and sexuality and teaching them the use of slow abdominal breathing (for hot flashes), the use of Kegel pelvic-floor-muscle exercises (for urinary incontinence and sexual response), and the use of moisturizers such as Replens and lubricants such as Astroglide (for vaginal dryness).
Also, patients with particular psychosocial stressors benefit from referral to counseling or to support groups.