380
Citationsfrom the Literature
in predictable absorption without major intermediary metabolism, whereas all oral estrogens are subject to intestinal metabolism before entering the systemic circulation. Various options are available. Injectable estrogens, because of rapid absorption and metabolism, are impractical for long-term replacement therapy. The primary drawback to subcutaneous estradiol pellets is the surgical procedure required for their insertion and removal. Vaginal epithelium is an effective pathway for absorption of estrogen given by solution, tablet, or cream, although only the latter is currently approved for clinical use; relatively constant serum levels of estradiol can be obtained with vaginal rings. Transdermal patches provide controlled hormone levels for up to 3.5 days. Although oral conjugated equine estrogens have been used extensively, they introduce types of estrogen, such as equilin, that are not naturally found in humans and that can produce a pronounced hepatic response. Micronized estradiol, oral estrone, and other estrogens have been used as alternatives to equine estrogens. Clinicians should understand the pharmacokinetics of the various options for replacement therapy and select a course of treatment that is safe, effective, and convenient for the patient. Enhancing patient compliance with hormone replacement therapy at menopause Nachtigall LE New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA OBSTET GYNECOL 1990,75/4 SUPPL (77S-80s) Physicians who prescribe hormone replacement therapy for menopausal women should explain the purpose, risks, and side effects of the treatment. This enhances compliance and discourages patients from discontinuing therapy because of fears of cancer or misconceptions about hormone replacement therapy. The physician should explain that the risk of endometrial cancer is virtually eliminated (reduced to that of a normal woman or a woman not receiving therapy) by the addition of progestogen to estrogen regimens, and that when this cancer does occur, it is usually diagnosed and treated early. Recent studies have not conclusively shown a significant effect of progestogen on lipid profiles relevant to cardiovascular disease. Hormone replacement therapy does not appear to be associated with an increased risk of breast cancer. Nuisance side effects (such as edema and breast tenderness) can be better tolerated if the physician prepares the patient, offers a solution, and helps to put the problem in perspective. Other measures, such as providing written information and avoiding unnecessary biopsies, also enhance compliance. Physiology and treatment of hot flushes Ravnikar V Division of Vincent Reproductive Endocrine, Infertility, and Menopause, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA OBSTET GYNECOL l!J90,75/4 SUPPL (3S--8s) Objective measures of vasomotor flushes have clarified their biologic basis and have established the peripheral re2ctions as compensatory mechanisms for hypothalamic thermoInt J Gynecol Obstet 33
regulatory instability. Subsequently, investigations into the pathogenesis of flushes pointed to increasingly higher levels of control. The observed relationship between estrogen deprivation and vasomotor instability led to the hypothesis of a causeeffect relationship with LH and FSH. However, patients with pituitary insufficiency were found to have hot flushes despite a lack of LH and FSH secretion. Hypothalamic secretion of gonadotropin-releasing hormone (GnRH) was studied for possible correlation with vasomotor episodes. Patients with and without symptoms had similar levels of LH secretion, but those who had symptoms and were closer to menopause had higher peripheral levels of immunoreactive GnRH, implying involvement of a hypothalamic mechanism, although not a causeeffect relationship. With prolonged estrogen deficiency, immunoreactive GnRH levels decline. Vasomotor episodes occur after estrogen withdrawal in subgroups of patients without appreciable secretion of GnRH, although LH and FSH secretions remain elevated. Vasomotor flushes are treated most effectively with estrogen. Agents such as medroxyprogesterone acetate and lofexidine may reduce the incidence of flushes. Cardiovascular implications of estrogen replacement therapy Lobo RA Department of Obstetrics and Gynecology, University of Southern California Medical Center, Los Angeles, CA, USA OBSTET GYNECOL 1990,75/4 SUPPL (l&S-25s) Estrogen appears to protect against the development of cardiovascular disease, the leading cause of death in women, by a number of mechanisms. The protective effect is believed to be mediated principally by beneficial changes in cholesterol levels. Estrogen decreases low-density lipoprotein (LDL) cholesterol and increases high-density lipoprotein (HDL) cholesterol levels by mechanisms that include the possible induction of LDL receptors and the destruction of hepatic lipase, which degrades HDL cholesterol. However, estrogen also appears to have a direct beneficial effect on vessel-wall physiology. One of these effects may be an increase in local prostacyclin production. The type of estrogen used in hormone replacement therapy and the route of administration determine the positive and negative effects of estrogen on the cardiovascular system. In general, synthetic estrogens, because they are manyfold more potent than natural estrogens, should not be used. Most studies show a 50% or greater reduction in cardiovascular disease and related mortality with postmenopausal estrogen administration. There is no evidence that postmenopausal estrogen replacement adversely affects carbohydrate metabolism, blood pressure, or coagulation. By use of a mathematical model to study the overall effects of estrogen therapy, it can be shown that more lives can be saved from the reduction in cardiovascular disease with estrogen use than from the reduction in death from osteoporosis or any other disease state affected by estrogen. Serious consideration has to be given to the cardiovascular effects of added progestogen, which may attenuate or eliminate the beneficial effects of estrogen on HDL, cholesterol. If used in low doses and only in those women with an intact uterus, progestogens may not exert this negative effect on cardiovascular function.
Citationsfrom the Literature
in predictable absorption without major intermediary metabolism, whereas all oral estrogens are subject to intestinal metabolism before entering the systemic circulation. Various options are available. Injectable estrogens, because of rapid absorption and metabolism, are impractical for long-term replacement therapy. The primary drawback to subcutaneous estradiol pellets is the surgical procedure required for their insertion and removal. Vaginal epithelium is an effective pathway for absorption of estrogen given by solution, tablet, or cream, although only the latter is currently approved for clinical use; relatively constant serum levels of estradiol can be obtained with vaginal rings. Transdermal patches provide controlled hormone levels for up to 3.5 days. Although oral conjugated equine estrogens have been used extensively, they introduce types of estrogen, such as equilin, that are not naturally found in humans and that can produce a pronounced hepatic response. Micronized estradiol, oral estrone, and other estrogens have been used as alternatives to equine estrogens. Clinicians should understand the pharmacokinetics of the various options for replacement therapy and select a course of treatment that is safe, effective, and convenient for the patient. Enhancing patient compliance with hormone replacement therapy at menopause Nachtigall LE New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA OBSTET GYNECOL 1990,75/4 SUPPL (77S-80s) Physicians who prescribe hormone replacement therapy for menopausal women should explain the purpose, risks, and side effects of the treatment. This enhances compliance and discourages patients from discontinuing therapy because of fears of cancer or misconceptions about hormone replacement therapy. The physician should explain that the risk of endometrial cancer is virtually eliminated (reduced to that of a normal woman or a woman not receiving therapy) by the addition of progestogen to estrogen regimens, and that when this cancer does occur, it is usually diagnosed and treated early. Recent studies have not conclusively shown a significant effect of progestogen on lipid profiles relevant to cardiovascular disease. Hormone replacement therapy does not appear to be associated with an increased risk of breast cancer. Nuisance side effects (such as edema and breast tenderness) can be better tolerated if the physician prepares the patient, offers a solution, and helps to put the problem in perspective. Other measures, such as providing written information and avoiding unnecessary biopsies, also enhance compliance. Physiology and treatment of hot flushes Ravnikar V Division of Vincent Reproductive Endocrine, Infertility, and Menopause, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA OBSTET GYNECOL l!J90,75/4 SUPPL (3S--8s) Objective measures of vasomotor flushes have clarified their biologic basis and have established the peripheral re2ctions as compensatory mechanisms for hypothalamic thermoInt J Gynecol Obstet 33
regulatory instability. Subsequently, investigations into the pathogenesis of flushes pointed to increasingly higher levels of control. The observed relationship between estrogen deprivation and vasomotor instability led to the hypothesis of a causeeffect relationship with LH and FSH. However, patients with pituitary insufficiency were found to have hot flushes despite a lack of LH and FSH secretion. Hypothalamic secretion of gonadotropin-releasing hormone (GnRH) was studied for possible correlation with vasomotor episodes. Patients with and without symptoms had similar levels of LH secretion, but those who had symptoms and were closer to menopause had higher peripheral levels of immunoreactive GnRH, implying involvement of a hypothalamic mechanism, although not a causeeffect relationship. With prolonged estrogen deficiency, immunoreactive GnRH levels decline. Vasomotor episodes occur after estrogen withdrawal in subgroups of patients without appreciable secretion of GnRH, although LH and FSH secretions remain elevated. Vasomotor flushes are treated most effectively with estrogen. Agents such as medroxyprogesterone acetate and lofexidine may reduce the incidence of flushes. Cardiovascular implications of estrogen replacement therapy Lobo RA Department of Obstetrics and Gynecology, University of Southern California Medical Center, Los Angeles, CA, USA OBSTET GYNECOL 1990,75/4 SUPPL (l&S-25s) Estrogen appears to protect against the development of cardiovascular disease, the leading cause of death in women, by a number of mechanisms. The protective effect is believed to be mediated principally by beneficial changes in cholesterol levels. Estrogen decreases low-density lipoprotein (LDL) cholesterol and increases high-density lipoprotein (HDL) cholesterol levels by mechanisms that include the possible induction of LDL receptors and the destruction of hepatic lipase, which degrades HDL cholesterol. However, estrogen also appears to have a direct beneficial effect on vessel-wall physiology. One of these effects may be an increase in local prostacyclin production. The type of estrogen used in hormone replacement therapy and the route of administration determine the positive and negative effects of estrogen on the cardiovascular system. In general, synthetic estrogens, because they are manyfold more potent than natural estrogens, should not be used. Most studies show a 50% or greater reduction in cardiovascular disease and related mortality with postmenopausal estrogen administration. There is no evidence that postmenopausal estrogen replacement adversely affects carbohydrate metabolism, blood pressure, or coagulation. By use of a mathematical model to study the overall effects of estrogen therapy, it can be shown that more lives can be saved from the reduction in cardiovascular disease with estrogen use than from the reduction in death from osteoporosis or any other disease state affected by estrogen. Serious consideration has to be given to the cardiovascular effects of added progestogen, which may attenuate or eliminate the beneficial effects of estrogen on HDL, cholesterol. If used in low doses and only in those women with an intact uterus, progestogens may not exert this negative effect on cardiovascular function.
