Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Symptoms due to estrogen deficiency begin in the perimenopausal years and progress as serum levels of this hormone decrease Vasomotor instability, manifested by hot flushes or night sweats, may persist for several months to a few years. Psychologic symptoms include anxiety, tension, depression, insomnia, palpitations, and headaches. Atrophy of the genital epithelium may result in senile vaginitis with symptoms of irritation, burning, pruritus, dyspareunia, and even vaginal bleeding. Even the lower urinary tract mucosa is dependent upon estrogen. Postmenopausal osteoporosis affects 25 to 50% of older women and increases the risk for vertebral, hip, and other fractures. Estrogen therapy for menopausal complaints has received adverse publicity because several reports have indicated that unopposed estrogens increase the risk of endometrial cancer. Added progestogen not only negates this risk but reduces the incidence of endometrial adenocarcinoma in estrogen-progestogen users to less than that observed in untreated women. Estrogen replacement therapy does not increase the risk of breast cancer; the incidence of this malignancy, however, was also less in the estrogen-progestogen users when compared with either the untreated women or from that expected from the national cancer surveys. In evaluating postmenopausal women for hormone replacement, the benefits of estrogen-progestogen therapy must be weighed against possible risks.
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PMID:The menopause. 351 23

This review briefly outlines the pharmacology of natural and synthetic estrogens, and synthetic progestins, and summarizes their beneficial and adverse effects for contraceptive and menopausal therapy. Currently, oral contraceptives contain 30-50 mc synthetic estrogen, and 1-5 mg nor-progestin; menopausal therapy may be either 0.625-1.25 mg natural estrogen or estrogen plus 10 mg medroxyprogesterone acetate daily if the woman has her uterus. The biologic effects of estrogens are : decrease in lipoproteins, increased blood coagulation factors, increased blood pressure, decreased glucose tolerance. Progestins increase blood lipids and increase insulin and glucose. Oral contraceptives increase the risk of cardiovascular disease, particularly in smokers and in women over 35, in proportion to dose. These studies should be recapitulated in more detail with the newer low-dose pills. Orals have far more beneficial effects, besides providing an inexpensive, effective method contraception. The death rate of users of oral contraceptives is 3.7/100,000 (1.8 in nonsmokers and 6.5 in smokers), but the risk is 5.5 times higher in nonusers exposed to pregnancy and childbirth. The risk for users of barrier methods backed up by abortion is lower, but pills are cheaper and more acceptable. If woman did not take oral contraceptives, they would not be protected from cancer of the breast, ovary, endometrium, and ovarian and breast cysts. Menopausal therapy puts woman at increased risk of endometrial cancer only if the estrogen is taken alone, not if progestin is combined with the estrogen. There are no other adverse effects except decreased glucose tolerance and possible comprise of lipoproteins if a norprogestin of menopausal estrogens effectively treat hot flashes, depression, vaginal atrophy and bones loss.
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PMID:The adverse effects of hormonal therapy. 351 31

This paper reviews both minor and major adverse reactions caused by estrogenic substances (natural and synthetic, steroidal and nonsteroidal) of which diethylstilbestrol is the prototype of nonsteroidal synthetic estrogen. Minor side effects include nausea, breast tenderness, and excessive cervical secretions (most common), headache, and water and salt retention (less common and often eradicated by lowering estrogen dosage). Vertigo, yeast infections, depression, and photosensitivity are other minor effects. Major side effects are discussed in some detail. Major effects include those on the endocrine system (e.g., feminization in boys and men and precocious puberty in girls); breast tumors; endometrial carcinoma; ovarian tumors; hypertension; thromboembolism; blood clotting excesses; various metabolic effects (including lipid metabolism and carbohydrate metabolism alterations); liver changes (bile alterations and neoplasms); porphyria; melanoma; and effects on a fetus in situ during maternal estrogen administration. In general, lowering doses of estrogen should help eradicate or alleviate most of these effects.
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PMID:Clinical toxicology of estrogens. 741 28

Recent cohort and case control studies of low-dose combined oral contraceptives (COCs) containing the new generation of progestogens have allowed classification of adverse effects into those which are rare but serious and should be considered risks and those which are more frequent but are less of a threat to health. Low-dose COCs continue to affect coagulation in a complex way, but the risk is less than with the older preparations, and it can be minimized by screening women for a personal or familial history of early or unusual thrombosis and for levels of protein C, S, and antithrombin III. Women with true migraine with focal signs should also avoid using COCs. The relative risk of myocardial infarction (MI) may increase from 4:1 in women with one risk factor (age, smoking, hypertension, hyperlipidemia, and diabetes) to 20:1 with two risk factors and 128:1 with three or more risk factors. In the absence of all risk factors, a recent study indicated that the relative risk of MI with COC use was 1.9 for current and past use. COC use also causes a slight increase in hypertension in most women, especially those who are older or have a family history of hypertension. While the COC can affect carbohydrate and lipid metabolism, the new generation of progestogens has reduced these effects. The COC may accelerate presentation of gallbladder disease in predisposed women. The COC protects against benign breast disease but may increase the risk of breast cancer and cervical cancer slightly. There is a strong link between hepatocellular adenoma and COC use, but the incidence is low. Return to fertility after use has not been a problem. Both estrogenic adverse effects (nausea, dizziness, irritability, weight gain, bloating) and progestogenic adverse effects (vaginal dryness, acne, hirsutism, weight gain, depression, loss of libido) can occur in 50% of women, but these generally disappear after a few months of use. In conclusion, the low-dose, third generation COCs are associated with minimal risks in the absence of other risk factors and have many beneficial effects such as the prevention of ovarian and endometrial cancer; a decrease in pelvic inflammatory disease and ectopic pregnancies; and protection from anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease as well as from the morbidity and mortality associated with pregnancy.
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PMID:The combined oral contraceptive. Risks and adverse effects in perspective. 776 40

The US Food and Drug Administration finally approved the injectable contraceptive Depo-Provera (DMPA) in October 1992, 25 years after its introduction. Women return to a health facility every 90 days for an intramuscular injection of 150 mg DMPA, which provides them 99% effective contraception. Menstrual changes and spotting are the leading reasons for DMPA discontinuation. Eventually, more than 50% of DMPA users develop amenorrhea. During the first year, women gain about 2 kg and weight increases as time passes. Weight gain is the second leading reason for DMPA discontinuation. DMPA may adversely affect glucose tolerance in women at risk for diabetes, but it does not affect cardiovascular or metabolic functions. It may increase the risk of osteoporosis. A rare side effect is convulsions. 1-10% of DMPA users have other central nervous system effects, such as headaches, dizziness, and depression. Itching and rashes may develop. Fertility returns within 1 year after discontinuation. DMPA is linked to low birth weight. It apparently does not harm breast-fed infants or hinder lactation. A World Health Organization study shows that DMPA users less than 35 years old experience a slight increase in breast cancer but a reduced incidence of endometrial cancer. Nurses are instrumental in guiding women as they choose DMPA and in informing them about its potential side effects, including breast cancer risk. They must screen women for pregnancy and evaluate their risk of breast cancer. They must determine whether women are able to return every 3 months for DMPA injections. Women who select DMPA must use other contraception, e.g., barrier protection, within the first 24 hours after initial injection. Nurses should counsel them about the likely menstrual changes to reduce the likelihood of dissatisfaction. They should recommend a daily dose of 1200 mg of elemental calcium and daily exercise of long bones to minimize the risk of developing osteoporosis.
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PMID:Depo-Provera. 849 47

As more women are living longer, there is an increasing need for women to discuss hormone replacement therapy (HRT) with their physicians. This task is complicated by areas of scientific uncertainty and evolving data concerning the risks and benefits of HRT. Benefits of HRT that are supported by strong scientific evidence include relief from menopausal symptoms such as hot flashes, prevention of osteoporosis, cardioprotective effects, relief of urogenital atrophy, and decreased urinary incontinence. Benefits supported by observational evidence include improvement of emotional lability and depression, improved sense of well-being in patients with rheumatoid arthritis, increased dermal and total skin thickness, improved verbal memory skills, and decreased risk of colon cancer. Risks to consider include a possible increase in the incidence of breast cancer and an increase in endometrial cancer in women who have an intact uterus and do not receive a progestin. Women in various risk groups, such as those at risk for coronary artery disease, osteoporosis, or breast cancer, must consider the risk-to-benefit ratio for their own individual circumstances.
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PMID:Current concepts in postmenopausal hormone replacement therapy. 869 Nov 83

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrogen receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In addition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine therapy for women with metastatic breast cancer. Tamoxifen, acting predominantly as an estrogen agonist in the liver, has generally favourable effects on serum lipids in postmenopausal women. In addition, tamoxifen has been shown to preserve bone mineral density and may even decrease the risk of osteoporosis in these women. Most patients treated with tamoxifen have minimal adverse effects. Vasomotor symptoms are the most commonly reported events. Less frequently, vaginal discharge or dryness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has been suggested in some adjuvant trials. Rarely, ocular toxicity and hepatotoxicity are found. The adverse effect of primary importance is the increased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage, similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefits of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all women with metastatic breast cancer. Should tamoxifen prove to be an effective chemopreventive agent for breast cancer, the risks and benefits of treatment will have to be more carefully assessed for this setting.
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PMID:Tamoxifen in postmenopausal women a safety perspective. 893 95

The preventive effect of estrogen on Alzheimer's disease (AD) has become clear with epidemiological data. Therapeutic effects of estrogen have not yet been established. In this presentation, we report our new basic and clinical data. The estrogen receptor, (ER)alpha, and ERbeta mRNA were investigated in rat brain. Estradiol-17beta (E(2)) treatment following OVX reduced the levels of ERalpha mRNA in the hypothalamus. In the substantia innominata (SI), the number of choline acetyltransferase immunoreacive cells increased significantly in the estrogen treatment rat. The neurons in SI projecting to the forebrain cortex contained ERalpha. Increasing amounts of intracellular calcium, peroxidation, and apoptosis with amyloid beta were suppressed in neuronal cells from rat pheochromocytoma (PC12) cells with E(2). ERalpha cDNA transfected PC 12 cells elaborated more neurite-like processes with E(2). In clinics, we are currently preparing vaginal progesterone tablets, which essentially may concentrate in the endometrium to prevent endometrial cancer, with few general circulation of progesterone inviting less depression. The therapeutic effects of cyclic estrogen, such as its preventive effect, are suggested in these studies, at least on mild AD.
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PMID:Alzheimer's disease and estrogen. 1138 81

Gynecologists use either oral or parenteral progestogens either alone or in combination with estrogens to treat various conditions. Parenteral routes of progestogen delivery are intramuscular injections, intravaginal pessaries, subcutaneous implants, and vaginal rings. Progestogens treat dysfunctional uterine bleeding by first controlling the acute bleeding episode and then by establishing normal ovulatory cycles. 1-2 tablets of medroxyprogesterone acetate (MPA)/day or 1-3 tablets of norethindrone/day should stop uterine bleeding in 72 hours. If not, 25 mg intravenous premarin should control it in 6-24 hours. Cyclical progestational (e.g., MPA) therapy for 3-6 cycles should establish normal ovulatory cycles. After appropriate laparoscopic staging by double puncture technique, progestogens can be used to treat mild-moderate endometriosis. Gynecologists should consider the following criteria when selecting the ideal progestin for hormone replacement therapy: adjustment of dosage of progestin and estrogen over 3-6 months to maintain the beneficial effects of the estrogen and to minimize the adverse effects of the progestin, progestin dosage sufficient to protect against endometrial hyperplasia and cancer, economical progestin, and minimization of weight gain, depression, oral intolerance, and androgenic action. Hydrogesterone and MPA meet these criteria. Oral contraceptives with a progestin and the smallest possible dose of estrogen are well-tolerated, cause no break-through bleeding, produce minimal side effects, and protect against pregnancy (99% contraceptive effectiveness rate). They also protect against endometrial cancer, endometriosis, premenstrual tension, dysmenorrhea, and irregular cycles. Intramuscular injections of progestins (MPA, NET-EN), subcutaneous levonorgestrel implant, and the levonorgestrel IUD are new contraceptive developments and provide a high degree of contraceptive efficacy. MPA at very high doses cause remission of breast endometrial lesions.
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PMID:Progestogens in gynaecological practice. 1217 92

Ever since a gradual but significant reduction in the estrogenic and progestogenic components of oral contraceptives (OCs) was made, there has been a corresponding decrease in adverse effects associated with the pill. The beneficial effects include prevention of pregnancy, reduction in pelvic inflammatory disease, protection against ovarian/endometrial cancer and benign breast tumors and ovarian cysts, reduction in the occurrence of rheumatoid arthritis among OC users, and regulation of the menstrual cycle. The adverse effects include diseases of the circulatory system (myocardial infarction, venous thromboembolism, subarachnoid hemorrhage, hypertension), possible carcinogenicity (breast, cervix, melanoma), pituitary adenomas, liver disorders, glucose metabolix effects (diabetes), vitamin status alteration, delay in return of menstruation and fertility, and a number of minor side effects (nausea, vomiting). Contraindications to OC use include history of malignancy of the breast or genital tract, venous thromboembolism, cerebrovascular accident, undiagnosed abnormal vaginal bleeding, focal migraine, or familial hyperlipidemia. The following situations require medical assessment before OCs are prescribed, and medical supervision if OCs are prescribed: age 40+, smoking and age over 35, mild hypertension or a history of hypertensive disease of pregnancy (toxemia), epilepsy, diabetes mellitus, history of bouts of depression, history of oligomenorrhea or amenorrhea in nulliparous women, and gallbladder disease. Problems could occur with OC use in the following situations: 1) lactation (ideally, OCs should be withheld until the child is weaned but if not possible, OCs should not be given until lactation is established); 2) drug interaction (other contraceptive form should be used when the patient is taking antibiotics or anticonvulsants); 3) tropical diseases (studies are still underway); 4) adolescence (very young girls should use other contraceptive method until regular menstruation is established); 5) postcoital contraception (limited use of steroids in emergency situation); and 6) hormonal pregnancy tests (use of oral steroids for pregnancy testing is not recommended). The 3 main types of OCs currently used are the combined estrogen and progestagen, the progestagen-only OC, and the triphasic OC. The lowest effective dose of a compound should be used, and healthy women may continue to use OCs for many years.
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PMID:Statement on steroidal oral contraceptives. 1226 73


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