Hypertension induced by pregnancy, oral contraceptives, and postmenopausal replacement therapy

Hypertension may develop during pregnancy or with the use of OC pills. Although the precise manner by which this rise in blood pressure occurs is unknown, appropriate management of the problem can protect against the consequences. The use of hormonal replacement therapy after menopause is not associated with a rise in blood pressure, and appears to provide significant protection against CHD.     

Exogenous estrogen in systemic lupus erythematosus: oral contraceptives and hormone replacement therapy

The role of exogenous estrogen in the initiation and maintenance of human SLE remains very controversial. Although cohort studies suggest an increase in the incidence of SLE with both oral contraceptives and hormone replacement therapy, recent retrospective studies suggest that the risk of flare is not increased with hormone replacement therapy. However, exogenous estrogen does increase hypercoagulability, an issue in SLE patients with antiphospholipid antibodies. The prospective SELENA study will ultimately address whether exogenous estrogen increases severe flares in SLE.     

Hepatic adenomas and oral contraceptives.

Over the past 5 years there has been an increase in the number of reports of patients with hepatic adenomas, and an association has been found between these tumors and the use of oral contraceptives. Up to January 1975 46 patients have been reported with this association. The histology of the tumors varies, with several names having been applied to the variations. Adenoma or focal nodular hyperplasia seem to be the most appropriate terms. Most of the commonly used oral contraceptives have been involved. Usually the use of the contraceptive has been at least 2 years. In 1 case, adenoma was diagnosed 4 years after stopping use of the drug. Symptoms have been abdominal pain and an abdominal mass. The tumor may rupture with hemorrhage into the abdominal cavity creating an emergency. Hepatic arteriography has been used to make an early diagnosis. Biochemical tests remain normal. Needle biopsy is contraindicated; surgery is indicated, however. The lesion may be multiple. Hepatic adenoma should be suspected in any young woman with abdominal pain and enlargement of the liver. Ruptured hepatic adenoma should be considered in acute abdominal emergencies, in young women who are taking oral contraceptives, and in older women taking hormone replacements.     

The effect of oral contraceptives and estrogen replacement therapy on the risk of rheumatoid arthritis: a population based study

OBJECTIVE: Epidemiologic evidence for a protective effect of exogenous female sex hormones on the development of rheumatoid arthritis (RA) is contradictory. We examined whether exposure to either oral contraceptives (OC) or postmenopausal estrogen replacement therapy (ERT) is associated with the development of RA in women. METHODS: We separately examined the relationship between use of OC and ERT on the risk of RA in a population based case-control study. Case patients, including all female residents of Rochester, Minnesota, > or = 18 years of age, who first fulfilled 1987 American College of Rheumatology criteria for RA between 1955 and 1994 (n = 445), were compared with age matched female controls from the community. Multivariable conditional logistic regression models were used to determine whether OC or ERT exposure had an effect on RA development after controlling for potential confounders. RESULTS: We observed an inverse association between ever-use of OC and the risk of RA, which persisted after adjusting for potential confounders in multivariate analyses (OR 0.56, 95% CI 0.34, 0.92). Earlier calendar-year of first exposure to OC was associated with lower OR for RA. We found no evidence of a significant association of ERT with RA risk (adjusted OR 1.11, 95% CI 0.69, 1.78). CONCLUSION: Exposure to OC, but not ERT, significantly reduces the risk of development of RA. The risk of developing RA is lower when OC exposure occurred in earlier years, which suggests that the higher doses of estrogens and progestins contained in earlier OC preparations may have a stronger protective effect against developing RA. While this protective effect is strong, it only explains a small portion of the observed decrease in RA incidence over the past few decades because the proportion of Rochester women exposed to OC is quite small.     

Effect of gender differences and estrogen replacement therapy on vascular reactivity

The incidence of cardiovascular disease is lower in premenopausal women compared with men; following menopause, the risk of mortality from cardiovascular disease increases in females. Postischemic dilatation of the brachial artery has been used previously as an index of endothelium-mediated vasodilation. Using this index, we examined a group of premenopausal and postmenopausal women, some of whom were on estrogen replacement therapy (ERT). All subjects were normotensive (blood pressure [BP] <140/90 mm Hg) and normoglycemic (blood glucose, <100 mg/dL). Fourteen healthy women (mean age, 27 +/- 0.8 years; mean total cholesterol, 174 +/- 6.7 mg/dL) and fourteen healthy men (mean age, 26 +/- 1.4 years; mean total cholesterol, 181 +/- 7.2 mg/dL) were investigated. Nineteen postmenopausal women were also examined; 11 were on ERT (mean age, 55 +/- 2.1 years; mean total cholesterol, 213 +/- 6.6 mg/dL) and eight were not on ERT (mean age, 60 +/- 3.6 years; mean total cholesterol, 222 +/- 14.4 mg/dL). Ischemia was induced by inflating a cuff over the forearm to a pressure of 40 mm Hg above systolic for 5 minutes. Doppler ultrasonography (Acuson [Mountain View, CA] 128XP/10c ultrasonograph with a 7.5-MHz linear array transducer) was used to measure the brachial artery diameter before inflation and 15 seconds and 45 to 60 seconds following cuff deflation. Flow-mediated dilatation (FMD%) and hyperemia were defined as the percentage increase over basal diameter and basal flow, respectively. Postischemic median dilatation in men was 4.20% (interquartile range, 2.13% to 5.56%) and 11.48% (interquartile range, 8.70% to 14.29%) in age-matched premenopausal women (P < .01). For women on ERT, the postischemic median dilatation was 8.11% (interquartile range, 6.01% to 11.60%), as compared with 2.82% (interquartile range, 1.32% to 3.28%) for women without ERT (P < .01). Premenopausal women showed significantly greater dilatation after ischemia than postmenopausal women without ERT (P < .0001). Hyperemia was similar in all groups. These findings show that postischemic vasodilation of the brachial artery is greater in premenopausal women versus age-matched men; it is decreased in postmenopausal women, and ERT restores it toward normal. The pathophysiology underlying the diminution in postischemic dilatation may be relevant to atherogenesis and coronary artery disease (CAD).     

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Effects of the menopause, gender, and estrogen replacement therapy on vascular nitric oxide activity

Changes in vascular nitric oxide (NO) activity may contribute to cardiovascular risk. We determined the effect of the menopause, gender, and estrogen replacement therapy on arterial vascular NO activity. Vascular NO activity and sensitivity were determined in 15 healthy premenopausal women (mean age, 48 yr), 12 postmenopausal women (51 yr), and 14 men (51 yr). The effects of 14 days of estrogen replacement therapy (625 microg conjugated estrogens) were studied in 20 healthy postmenopausal women (60 yr). Forearm blood flow responses to brachial arterial infusions of L-NG-monomethyl-arginine (L-NMMA), norepinephrine, glyceryl trinitrate (GTN), and serotonin were determined using venous occlusion plethysmography. Constrictor responses to L-NMMA were reduced in postmenopausal women (82 +/- 14, summary response, mean +/- SEM) and men (89 + 6) compared to premenopausal women (118 + 10; P < 0.05). Constrictor responses to norepinephrine were increased in males (125 +/- 13) compared to premenopausal (81 +/- 8) and postmenopausal (88 +/- 16) women (P < 0.05). No differences were observed in GTN or serotonin responsiveness. Constrictor responses to L-NMMA increased after estrogen replacement (132 +/- 7 vs. 89 +/- 14; P < 0.05), with no change in norepinephrine, GTN, or serotonin responses. The menopause and male gender were associated with reduced arterial NO activity. Two weeks of estrogen replacement therapy restored vascular NO activity to premenopausal levels. Changes in vascular NO activity may contribute to changes in cardiovascular risk associated with male gender, postmenopausal status, and estrogen replacement therapy. Increased alpha-adrenoceptor responsiveness may contribute to increased cardiovascular risk in males.     

Hepatic infarction related to oral contraceptive use

The first case of oral contraceptive (OC)-related common hepatic artery thrombosis with subsequent hepatic infarction is reported. Hepatic complications of OC use are enumerated and the clinical manifestation of hepatic infarction is described. Propranolol hydrochloride, because of its effect on liver blood flow, may have contributed to this disease process.     

Immunogenicity and the vascular risk of oral contraceptives

Data concerning circulating immune complexes were obtained for women who had had a pulmonary embolism, myocardial infarction, or cerebral thrombosis, and for 224 healthy controls. In women with pulmonary embolism who had used oral contraceptives concentrations of circulating immune complexes were significantly higher than in healthy controls (regardless of oral contraceptive use), or in those with pulmonary embolism who had never used these preparations. Concentrations of circulating immune complexes were not raised in myocardial infarction, but these women had major risk factors for ischaemic heart disease. The group of patients with cerebral thrombosis without risk factors tended to have high concentrations of circulating immune complexes. The data provide some confirmation that immunological mechanisms may play a role in thrombotic episodes associated with oral contraceptives, especially when they occur in the absence of risk factors for vascular disease.     

Immunogenicity and the vascular risk of oral contraceptives.

Data concerning circulating immune complexes were obtained for women who had had a pulmonary embolism, myocardial infarction, or cerebral thrombosis, and for 224 healthy controls. In women with pulmonary embolism who had used oral contraceptives concentrations of circulating immune complexes were significantly higher than in healthy controls (regardless of oral contraceptive use), or in those with pulmonary embolism who had never used these preparations. Concentrations of circulating immune complexes were not raised in myocardial infarction, but these women had major risk factors for ischaemic heart disease. The group of patients with cerebral thrombosis without risk factors tended to have high concentrations of circulating immune complexes. The data provide some confirmation that immunological mechanisms may play a role in thrombotic episodes associated with oral contraceptives, especially when they occur in the absence of risk factors for vascular disease.     

Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women

Menopause is associated with decreased lean body mass and increased fat due to aging and declining hormone secretion. Estrogens or estrogen-progestins have been used to alleviate vasomotor symptoms. However, estrogen-androgen (E/A) therapy is also used for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass. The objective of this 16-wk, double-blind, randomized, parallel group clinical trial was to compare esterified estrogen plus methyltestosterone (1.25 mg estrogen + 2.5 mg methyltestosterone/d; E/A group) vs. esterified estrogen alone (1.25 mg/d; E group) on body composition. Forty postmenopausal women (mean age, 57 yr) participated. Compared with estrogen treatment alone, women in the E/A group increased their total lean body mass and reduced their percentage fat for all body parts (P < 0.05). After E/A treatment, there were statistically significant increases in lean body mass by 1.232 kg [0.181 +/- 0.004, 0.81 +/- 0.057, and 0.24 +/- 0.009 kg in the upper body (P = 0.021), trunk (P = 0.001), and lower body (P = 0.047), respectively]. In the E group, the increase was 0.31 +/- 0.004, 0.021 +/- 0.03, and 0.056 +/- 0.05 kg in the upper body, trunk, and lower body, respectively. In the E/A group, body fat was reduced by 0.90 kg (P = 0.18 for the trunk only), and percentage body fat declined by 7.4% (P < or = 0.05 for all body parts). Lower body strength increased by 23.1 kg (51 lb) in the E/A group vs. only 11 kg (24.25 lb) in the E group (P = 0.002 between groups). A statistically significant increase in weight (2.7 +/- 5.1 vs. 0.1 +/- 4.6 lb; P < 0.05) was observed in the E/A group compared with the E group. When subjects were given self-reporting questionnaires, more improvement was noted in sexual functioning and quality of life in the E/A group when compared with patients receiving E alone. There were no noteworthy side effects. In conclusion, E/A replacement therapy can improve body composition, lower-body muscle strength, quality of life, and sexual functioning in postmenopausal women.     

Reversible mesenteric vascular occlusion associated with oral contraceptives

Reversible mesenteric vascular occlusion should be considered in young women on oral contraceptives who present with abdominal pain and bloody diarrhea. A patient is described in whom these symptoms as well as small bowel changes on x-ray resolved spontaneously only after discontinuation of the contraceptives. During the acute illness, thickened mucosa with rigidity of the bowel loops, narrowing of the bowel lumen, and thumb printing were evident on small bowel series.     

Estrogen replacement therapy, atherosclerosis, and vascular function

There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (>65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women or monkeys in the early stages of atherosclerosis progression has marked beneficial effects. Whether progestogens attenuate the cardiovascular benefits of estrogen replacement therapy has been controversial for more than a decade. Current evidence from studies of both monkeys and women suggest little or no attenuation of estrogen benefits for coronary artery atherosclerosis. Lack of compliance with estrogen replacement therapy, usually because of fear of breast cancer, remains a major problem. Future regimens may overcome that fear by the co-administration of a breast cancer preventive agent (i.e., selective estrogen receptor modulators, phytoestrogens) with low dose estrogen.