Use Of Exogenous Sex Hormones Research Articles

A Major Locus Influencing Plasma High-Density Lipoprotein Cholesterol Levels in the San Antonio Family Heart Study

To detect and measure the effects of a single locus on quantitative variation in plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical genetic analyses on data from 526 Mexican American individuals in 25 randomly ascertained pedigrees. By using maximum-likelihood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, standard deviations, relative frequency of a low HDL-C allele, and heritability for plasma HDL-C levels, plus the effects of sex (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex hormone use, and menopausal status under an unrestricted general model. Inclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21% of the variance, the detected major locus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter estimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P < .05), apoB (P < .01), hepatic lipase (P < .001), lipoprotein lipase (P < .001), and the LDL receptor (P < .001). While not excluding the apoE locus (LOD = -0.348, P < .21), the analysis provided no support for tight linkage between it and the detected major locus.

Exogenous sex hormones and the risk of rheumatoid arthritis : Arthritis Rheum. 1990 33/7 (947–953)

The use of exogenous sex hormones in relation to the risk of rheumatoid arthritis (RA) was examined in a cohort of married nurses ages 30-55 followed since 1976 in the Nurses Health Study. Baseline information on the use of oral contraceptives (OCs) replacement estrogens and other potential risk factors was obtained in 1976 and updated every 2 years. During 8 years of followup 217 incident cases of polyarthritis were ascertained (115 RA and 102 undifferentiated polyarthritis). When compared with women who had never used OCs the age-adjusted relative risk was 1.0 (95% confidence interval [CI] 0.7-1.3) for past users; however too many women were currently using OCs for a reliable estimate of its effect. Among postmenopausal women 123 cases of RA were reported. Compared with postmenopausal women who had never used replacement estrogens current users had an age-adjusted relative risk of 1.3 (95% CI 0.9-2.0) past users had an age-adjusted relative risk of 0.7 (95% CI 0.5-1.2) and ever-users had a relative risk of 1.0 (95% CI 0.7-1.4). These data do not show a protective effect of past use of OCs or replacement estrogens for RA; however a modest protective effect of current OC use cannot be excluded. (authors)

Exogenous sex hormones and the risk of rheumatoid arthritis

The use of exogenous sex hormones in relation to the risk of rheumatoid arthritis (RA) was examined in a cohort of married nurses 30-55 years of age followed since 1976 in the Nurses' Health Study. Baseline information on the use of oral contraceptives, replacement estrogens, and other potential risk factors was obtained in 1976 and updated every 2 years. During 8 years of followup, 217 incident cases of polyarthritis were ascertained (115 RA and 102 undifferentiated polyarthritis). When compared with women who had never used oral contraceptives, the age-adjusted relative risk was 1.0 (95% confidence interval [CI] 0.7-1.3) for past users; however, too few women were currently using oral contraceptives for a reliable estimate of its effect. Among postmenopausal women, 123 cases of RA were reported. Compared with postmenopausal women who never used replacement estrogens, current users had an age-adjusted relative risk of 1.3 (95% CI 0.9-2.0), past users had an age-adjusted relative risk of 0.7 (95% CI 0.5-1.2), and ever users had a relative risk of 1.0 (95% CI 0.7-1.4). These data do not show a protective effect of past use of oral contraceptives or replacement estrogens for RA; however, a modest protective effect of current oral contraceptive use cannot be excluded.

Blood pressure and endogenous testosterone in men

Exogenous sex hormone use, including oral contraceptives, post-menopausal hormonal therapy and anabolic steroids, has been associated with blood pressure changes in both sexes, but little is known about the relationship between blood pressure and endogenous sex hormones. We examined this relationship in men in the Rancho Bernardo population study. Out of 1132 men aged 30-79 years, those with hypertension, categorically defined as systolic blood pressure (SBP) greater than 160 mmHg and/or diastolic blood pressure (DBP) greater than 95 mmHg had significantly lower testosterone levels than non-hypertensives. Systolic and diastolic blood pressure inversely correlated with testosterone levels (r = 0.17, P less than 0.001 for systolic; r = -0.15, P less than 0.001 for diastolic) in the whole cohort. This association was present over the whole range of blood pressures and sex hormone levels with a stepwise decrease in mean SBP and DBP per increasing quartile of testosterone. Obesity accounted for some, but not all, of this relationship, which was reduced, but still apparent after adjusting for age and body mass index. No other hormone (androstenedione, estrone, estradiol) nor sex hormone-binding globulin showed a consistent relationship with blood pressure. The clinical and physiological significance of this relationship merits further investigation.

Exogenous Sex Hormone Exposure and the Risk for Major Malformations

Several studies have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. We conducted a case-control study of first-trimester sex hormone exposure among mothers of 1,091 infants with Down syndrome or at least one of 11 major malformations. For each malformation category, the infants with other malformations served as the control group. Associations were found between esophageal atresia and (1) any sex hormone exposure (odds ratio, 2.84); (2) progestins (odds ratio, 2.87); (3) nonspecified sex hormones (odds ratio, 2.99); and (4) hormonal pregnancy tests (odds ratio, 2.81). We found no potentially confounding variables for these associations. We found no statistically significant association between any malformation category and oral contraceptive exposure. Even if the relationship between esophageal atresia and noncontraceptive sex hormone exposure is causal, the absolute risk would be low, on the order of six per 10,000 exposed live births. ( JAMA 1986;255:3128-3132)

Exogenous sex hormone exposure and the risk for VACTERL association.

In several studies investigators have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. A group of malformations, the VACTERL (vertebral, anal, cardiac, trachea, esophageal, renal, limb-acronym) association, has been statistically associated with maternal exposure to exogenous sex hormones during the first trimester of pregnancy. The VACTERL association is a nonrandom group of major malformations that occur together more often than would be expected on the basis of chance. To assess this association, we conducted a case-control study of first-trimester exposure to sex hormones among mothers of 34 infants with the VACTERL association and of 1,024 comparison infants with one or more of ten major malformations or Down syndrome. The study subjects were malformed infants born between July 1970 and June 1979 and registered in a population-based birth defects registry. Information concerning the use of exogenous sex hormones during pregnancy was obtained by systematically interviewing the mothers of the malformed infants. Most of the mothers were interviewed within 6 months of their children's births. Each mother was interviewed within a year of her child's birth. We found an odds ratio of 0.98 (90% confidence limits 0.40, 2.38) for the relationship between VACTERL association and use of any sex hormone in the first trimester of pregnancy. Our study had adequate statistical power to detect a true relative risk of 2.8 or greater.

Exogenous Sex Hormone Exposure and the Risk for Major Malformations

Several studies have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. We conducted a case-control study of first-trimester sex hormone exposure among mothers of 1,091 infants with Down syndrome or at least one of 11 major malformations. For each malformation category, the infants with other malformations served as the control group. Associations were found between esophageal atresia and any sex hormone exposure (odds ratio, 2.84); progestins (odds ratio, 2.87); nonspecified sex hormones (odds ratio, 2.99); and hormonal pregnancy tests (odds ratio, 2.81). We found no potentially confounding variables for these associations. We found no statistically significant association between any malformation category and oral contraceptive exposure. Even if the relationship between esophageal atresia and noncontraceptive sex hormone exposure is causal, the absolute risk would be low, on the order of six per 10,000 exposed live births.

Maternal characteristics and hypospadias: a case-control study.

Various characteristics were compared among mothers of 99 singleton male live births (in Upstate New York, 1970-1974) with hypospadias and mothers of 99 singleton male live births, matched for maternal age, race, and residence. Maternal (and paternal) education, maternal height and weight, and the frequency of maternal diseases did not differ between cases and controls. Mean age at menarche was significantly later, but delayed menarche (16 years) was not more frequent, in case vs. control mothers. In the latest year during which the mother was neither pregnant nor taking oral contraceptives, menstrual cycles were significantly more often asymptomatic in case vs. control mothers, implying a higher frequency of anovulatory cycles in case mothers. This suggests the need for further studies on menstrual symptoms. Among case-control pairs with a previous pregnancy, the first pregnancy was less likely to have resulted in a male fetus in case vs. control mothers. Maternal use of exogenous sex hormones (oral contraceptives, hormone therapy, and hormone pregnancy tests) during the index pregnancy did not differ significantly between cases and controls, but the relative risk of 3.50 for hormone pregnancy tests (seven cases vs. two controls) was noteworthy in view of the results of previous studies.

Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study.

Total plasma lipid and lipoprotein-cholesterol distributions of 4756 white men and women between the ages of 20-59 are presented. Measurements were obtained during the visit-2 survey of the (LRC) Lipid Research Clinics Program Prevalence Study and correspond to a 15% random sample of 35748 white adults screened during the LRC visit-1 survey. Standardized examinations were carried out by 10 North American clinics using a common protocol on diverse target populations chosen to include a range of sociodemographic characteristics. Age-specific means medians and selected percentiles are given by sex with stratification on exogenous sex hormone use in women. Plasma lipid and lipoprotein concentrations in men and women vary with age. Differences in lipid and lipoprotein levels between the study populations are also present and manifest themselves as parallel trends of age-related changes in the 10 populations examined. Higher total cholesterol values in men as compared with women appear between the ages of 20-50 and higher LDL cholesterol between ages 20-55. VLDL cholesterol levels are similar in both sexes at ages 20 and 59 years but higher in men than in women in all intermediate age groups. HDL cholesterol is higher in women than in men throughout the age range under consideration. Women taking sex hormones have higher total cholesterol than women not on hormones between ages 20-50 and higher LDL cholesterol between 20-40. From the 3rd age decade onward HDL cholesterol levels are progressively higher in women taking hormones than in women who are not. Compared with women not taking exogenous sex hormones women taking hormones have higher total plasma triglyceride values at all ages from 20-59. VLDL cholesterol values are higher in women on hormones compared with nonusers of hormones younger than 55 years. (Authors modified)