Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most common cancer in the United States comprising 30% of all cancers. There is strong evidence indicating that cumulative estrogen, and possibly progesterone, exposure of breast epithelial cells causes this cancer. After age 40 the sharp increase of cancer rate slows considerably. In industrialized countries the rate is 6 times higher than in Asia or Africa, however, ethnicity does not seem to be a major factor, as shown by studies on Japanese migrants to the U.S. Early menarche, before age 12, increases the risk fourfold, and higher levels of estrogen and progesterone found in daughters of breast cancer victims. Strenuous physical activity could delay menarche to 15.4 years of age, thus lowering the risk. Menopause lowers the risk, too, as does a shorter active menstruation history. Increased parity also decreases the risk, late first full-term pregnancy does the opposite. In parous women prolactin levels are lower, and sex hormone-binding globulin (SHBG) levels are higher. In older age weight gain also becomes a contributory factor. Estrogen plays a strong role in the genesis of breast cancer, and estradiol levels were 30% higher in cancer patients. Urinary estrogen levels were 36% higher in North American teenagers than in Asians. Fat intake and reserpine use can increase prolactin levels, however, its role is only putative, as is the role of progesterone. Increasing duration of use of oral contraceptives also raises the risk depending on age at first use and duration. Estrogen replacement therapy is similarly implicated, although a combination estrogen- progesterone therapy was beneficial. Furthermore, the benefits of estrogen to prevent osteoporosis and heart disease also have to be balanced against its carcinogenic potential.
 ...
PMID:Endogenous and exogenous endocrine factors. 269 90

Plasma obtained and frozen in 1972-1974 from 1,009 white men (40-79 years old) who have been followed for 12 years was examined for endogenous sex hormone levels according to prevalent or subsequent cardiovascular disease. In these older men, no sex hormone measured (testosterone, androstenedione, estrone, or estradiol) was significantly associated with known cardiovascular disease at baseline or with subsequent cardiovascular mortality or ischemic heart disease morbidity or mortality. Sex hormone-binding globulin levels were also similar by disease status. Analyses of hormone:sex hormone-binding globulin ratios or of estrogen:androgen ratios showed a similar lack of association with cardiovascular disease. Testosterone levels were significantly inversely associated with levels of blood pressure, fasting plasma glucose, and triglyceride and body mass index. In contrast, the only significant estrogen risk factor associations were positive correlations of estrone with total plasma cholesterol, triglyceride, and glucose. These data do not support a causal role for elevated endogenous estrogen levels and heart disease.
 ...
PMID:Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. 340 97

In the polycystic ovary syndrome, hyperinsulinaemia is commonly found in women with hirsutism, oligomenorrhoea and acanthosis nigricans and this subset of patients possess adverse risk factors for coronary artery disease, particularly reduced HDL2 concentrations. Conversely, raised serum insulin concentrations are not common in women with PCOS in whom raised serum LH concentrations or regular menstrual cycles are present. We postulate that both direct ovarian and indirect actions of insulin (through changes in IGFI-I, IGFBP-I and SHBG concentrations) play important roles in determining androgen concentrations in women. Many intriguing questions follow from this link between the control of nutrition and reproduction and many old observations required re-examination in this new light. Vital to our understanding in this field will be the cause of moderate hyperinsulinaemia, the action of insulin on the normal ovary, and the importance of adverse surrogate risk factors for heart disease in hyperinsulinaemic women.
 ...
PMID:Clinical implications of hyperinsulinaemia in women. 828 79

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.
 ...
PMID:Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease. 895 51

The access of testosterone and estradiol to target tissues is regulated by sex hormone-binding globulin (SHBG) in human blood. Serum SHBG levels are low in patients with hyperandrogenism, especially in association with polycystic ovarian syndrome (PCOS) and in individuals at risk for diabetes and heart disease. Here, we identify SHBG coding region variations from a compound heterozygous patient who presented with severe hyperandrogenism during pregnancy. Serum SHBG levels in this patient measured 2 years after her pregnancy were exceptionally low, and her non-protein-bound testosterone concentrations greatly exceeded the normal reference range. A single-nucleotide polymorphism within the proband's maternally derived SHBG allele encodes a missense mutation, P156L, which allows for normal steroid ligand binding but causes abnormal glycosylation and inefficient secretion of SHBG. This polymorphism was identified in four other patients with either PCOS, ioiopathic hirsutism, or ovarian failure. The proband's paternal SHBG allele carries a single-nucleotide deletion within exon 8, producing a reading-frame shift within the codon for E326 and a premature termination codon. CHO cells transfected with a SHBG cDNA carrying this mutation fail to secrete the predicted truncated form of SHBG. To our knowledge, these are the first examples of human SHBG variants linked to hyperandrogenism and ovarian dysfunction.
 ...
PMID:Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction. 1192 24

We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studied 3,200 women, aged 42-52 yr, in the Study of Women's Health Across the Nation, a prospective multiethnic study of the menopausal transition. We measured the hemostatic factors, fibrinogen, factor VIIc, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), as well as glucose and insulin to calculate insulin resistance. After adjustment for body mass index, site, and ethnicity, SHBG was correlated with PAI-1 (partial r = -0.30) and t-PA (partial r = -0.12). Although testosterone was associated with t-PA (partial r = 0.13) and PAI-1 (partial r = 0.07), free androgen index was strongly correlated with t-PA (partial r = 0.18) and PAI-1 (partial r = 0.26). SHBG modified the association of hemostatic factors with insulin resistance. Women with greater insulin resistance had lower SHBG and higher PAI-1. Estrogen measures were not associated with insulin resistance. The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood. SHBG, which influences the amount of bioavailable hormone, significantly modified the association of PAI-1 and t-PA with insulin resistance. The longitudinal Study of Women's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women.
 ...
PMID:Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN. 1455 72