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Hormonal Contraception and Risk of Psychiatric and Other Noncommunicable Diseases in HIV-Infected Women.
Castilho JL, Jenkins CA, Shepherd BE, Bebawy SS, Turner M, Sterling TR, Melekhin VV
(2015) J Womens Health (Larchmt) 24: 481-8
MeSH Terms: Adult, Cohort Studies, Contraceptive Agents, Female, Contraceptives, Oral, Hormonal, Female, HIV Infections, Humans, Incidence, Medroxyprogesterone Acetate, Mental Disorders, Middle Aged, Retrospective Studies, Risk, Sexually Transmitted Diseases, Tennessee, Young Adult
Show Abstract · Added February 17, 2016
BACKGROUND - Hormonal contraception use is common among human immunodeficiency virus (HIV)-infected women. Risk of psychiatric and other noninfectious complications of hormonal contraception use has not been described in this population.
METHODS - We performed a retrospective cohort study of HIV-infected women receiving care in Tennessee from 1998 to 2008 to examine the risks of incident psychiatric and other noncommunicable diseases (NCDs), including cardiovascular, hepatic, renal, and malignant diseases, and hormonal contraception use, including depot medroxyprogesterone acetate (DMPA) and combined estrogen- and progestin-containing hormonal contraceptives. We used marginal structural models with inverse probability weights to account for time-varying confounders associated with hormonal contraception use.
RESULTS - Of the 392 women included, 94 (24%) used hormonal contraception during the study period. Baseline psychiatric disease was similar between women who received and did not receive hormonal contraception. There were 69 incident psychiatric diagnoses and 72 NCDs. Only time-varying DMPA use was associated with increased risk of psychiatric disease (adjusted odds ratio [aOR] 3.70; 95% confidence interval [95% CI] 1.32-10.4) and mood disorders, specifically (aOR 4.70 [1.87-11.8]). Time-varying and cumulative combined hormonal contraception use were not statistically associated with other NCDs (aOR 1.64, 95% CI 0.64-4.12 and aOR 1.16, 95% CI 0.86-1.56, respectively). However, risk of incident NCDs was increased with cumulative DMPA exposure (per year exposure aOR 1.45, 95% CI 1.01-2.08).
CONCLUSIONS - Among HIV-infected women, DMPA was associated with risk of incident psychiatric diseases, particularly mood disorders, during periods of use. Cumulative DMPA exposure was also associated with risk of other NCDs. However, combined estrogen and progestin-containing hormonal contraception use was not statistically associated with risk of any NCDs.
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16 MeSH Terms
Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.
McGlynn KA, Sahasrabuddhe VV, Campbell PT, Graubard BI, Chen J, Schwartz LM, Petrick JL, Alavanja MC, Andreotti G, Boggs DA, Buring JE, Chan AT, Freedman ND, Gapstur SM, Hollenbeck AR, Hou L, King LY, Koshiol J, Linet M, Palmer JR, Poynter JN, Purdue M, Robien K, Schairer C, Sesso HD, Sigurdson A, Wactawski-Wende J, Zeleniuch-Jacquotte A
(2015) Br J Cancer 112: 1266-72
MeSH Terms: Adult, Carcinoma, Hepatocellular, Cohort Studies, Contraceptives, Oral, Hormonal, Female, Humans, Liver Neoplasms, Middle Aged, Proportional Hazards Models, Prospective Studies, Reproductive History, United States
Show Abstract · Added March 17, 2015
BACKGROUND - Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women.
METHODS - In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248).
RESULTS - Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility.
CONCLUSIONS - The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.
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12 MeSH Terms
Relation of FGFR2 genetic polymorphisms to the association between oral contraceptive use and the risk of breast cancer in Chinese women.
Xu WH, Shu XO, Long J, Lu W, Cai Q, Zheng Y, Xiang YB, Dai Q, Zhao GM, Gu K, Bao PP, Gao YT, Zheng W
(2011) Am J Epidemiol 173: 923-31
MeSH Terms: Adult, Aged, Asian Continental Ancestry Group, Breast Neoplasms, China, Contraceptives, Oral, Hormonal, Disease Susceptibility, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 2, Risk Factors
Show Abstract · Added March 5, 2014
The fibroblast growth factor receptor 2 gene (FGFR2) has been associated with the risk of breast cancer in multiple ethnic populations, and its effect has been suggested to be hormone-dependent. A large, 2-stage, population-based case-control study was conducted in urban Shanghai, China, during the periods of 1996-1998 and 2002-2005. Exposure and genotyping information from 2,073 patients with breast cancer and 2,084 age-matched population controls was available for evaluation of the interactions between FGFR2 polymorphisms and exogenous estrogen exposure in the development of breast cancer. A logistic regression model was used to compute adjusted odds ratios and 95% confidence intervals. Of 20 genotyped and 25 imputed single nucleotide polymorphisms (SNPs), 22 were significantly associated with breast cancer. Three genotyped SNPs in close linkage disequilibrium, rs2303568, rs3135730, and rs1078806, and an imputed SNP of rs755793 in complete linkage disequilibrium with other 8 SNPs were observed to interact significantly with oral contraceptive (OC) use. The SNP-cancer association was evident only among OC users, and the OC use was only associated with the risk of breast cancer among carriers of these minor alleles at these loci. These findings suggest that genetic variants in FGFR2 may modify the role of OC use in causing breast cancer in Chinese women.
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14 MeSH Terms
Oral contraceptive use and breast cancer risk: modification by NAD(P)H:quinone oxoreductase (NQO1) genetic polymorphisms.
Fowke JH, Shu XO, Dai Q, Jin F, Cai Q, Gao YT, Zheng W
(2004) Cancer Epidemiol Biomarkers Prev 13: 1308-15
MeSH Terms: Adult, Age Distribution, Base Sequence, Breast Neoplasms, Case-Control Studies, China, Confidence Intervals, Contraceptives, Oral, Hormonal, Female, Genetic Predisposition to Disease, Humans, Incidence, Middle Aged, Molecular Sequence Data, NAD(P)H Dehydrogenase (Quinone), Odds Ratio, Polymerase Chain Reaction, Polymorphism, Genetic, Probability, Reference Values, Registries, Risk Assessment, Sensitivity and Specificity
Show Abstract · Added December 10, 2013
Despite intensive study, the relationship between oral contraception (OC) and breast cancer remains unclear. OCs contain a potent synthetic estrogen (ethinyl estradiol) but lower endogenous estradiol levels, and ethinyl estradiol is a weak progenitor of semiquinones, catechol estrogens capable of damaging DNA. NAD(P)H:quinone oxoreductase (NQO1) stabilizes semiquinones, thus potentially preventing genetic damage from catechol estrogens, and the NQO1 C609T polymorphism seems functionally relevant. Using data from the Shanghai Breast Cancer Study, a population-based case-control study, we investigated the relationships between OC use (20% ever using), breast cancer, and NQO1 (C/C 31% and C/T + T/T 69%) among 1,039 cases and 1,121 controls. Breast cancer was not significantly associated with NQO1 genotype. There was a significant protective association between OC after age 30 years and premenopausal breast cancer [odds ratio (OR) 0.51, 95% confidence interval (95% CI) 0.29-0.89] primarily with the NQO1 T allele (C/C OR 0.76, 95% CI 0.31-1.82; C/T + T/T OR 0.38, 95% CI 0.18-0.80; P for interaction = 0.19). The association between premenopausal breast cancer and OCs significantly differed with NQO1 genotype when using OCs for >18 months (C/C OR 2.34, 95% CI 0.92-5.99; C/T + T/T OR 0.69, 95% CI 0.38-1.25; P for interaction = 0.02). Among women with the C/C genotype, postmenopausal breast cancer was significantly associated with ever-using OCs (C/C OR 2.01, 95% CI 1.08-3.74; C/T + T/T OR 0.72, 95% CI 0.49-1.05; P for interaction < 0.01). This crossover was stronger with OC use prior to age 30 years (C/C OR 3.00, 95% CI 1.43-6.25; C/T or T/T OR 0.49, 95% CI 0.29-0.81; P for interaction < 0.01). Our results require confirmation but suggest that the OC and breast cancer association depends on the ability to invoke protection from catechol estrogens.
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4 Members
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23 MeSH Terms
Inhibition of oral contraceptive steroid-metabolizing enzymes by steroids and drugs.
Guengerich FP
(1990) Am J Obstet Gynecol 163: 2159-63
MeSH Terms: Animals, Contraceptives, Oral, Hormonal, Cytochrome P-450 CYP1A1, Cytochrome P-450 Enzyme Inhibitors, Ethinyl Estradiol, Humans, Hydroxylation, Norpregnenes, Progestins, Steroid Hydroxylases, Steroids
Show Abstract · Added March 5, 2014
The major 17 alpha-ethinyl estradiol 2-hydroxylase is humans is the hepatic enzyme cytochrome P-450 IIIA4 (P-450NF), which is known to be inducible by rifampicin or barbiturates. The literature indicates that 17 beta-estradiol, progesterone, and norgestrel are competitive inhibitors and that primaquine and tolbutamide are rather weak noncompetitive inhibitors. Recent experiments in this laboratory indicate that gestodene is a relatively potent mechanism-based inactivator of cytochrome P-450 IIIA4 in vitro. Inhibition requires incubation with the reduced form of nicotinamide adenine dinucleotide phosphate, is time and concentration dependent, and can be partially blocked by the presence of noninhibitory cytochrome P-450 IIIA4 substrates. The in vitro activation by gestodene provides a possible explanation for the increase in plasma estrogen levels reported in women administered gestodene along with 17 alpha-ethinyl estradiol.
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11 MeSH Terms