{"title":"Biologic and molecular mechanisms for sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics: Part II.","authors":"Marietta Anthony, Mary J Berg","doi":"10.1089/152460902760360568","DOIUrl":"10.1089/152460902760360568","url":null,"abstract":"<p><p>There are specific pharmacology issues related to women's unique physiology, including the hormonal changes that occur throughout their life span. Studies have shown alterations in drug metabolism in relation to phase of menstrual cycle, during pregnancy, or after menopause. In the brain, hormones can alter the response to drugs through various mechanisms. Estrogen and other compounds can bind to the estrogen receptor and modulate a wide range of activities within the cell. In addition, animal studies have demonstrated sexual dimorphism in the brain in terms of both the type of response to estrogen and the response as related to timing of administration. Many normal physiological changes that occur during pregnancy can affect pharmacokinetics and pharmacodynamics. These changes during pregnancy are dramatic rises in levels of estrogen and progesterone, increases in maternal blood volume, altered protein binding resulting from a drop in albumin levels, and a rise in levels of other plasma proteins. The field of chronobiology offers a way to study these changes in biological functions. Chronopharmacology is the study of how biological rhythms, particularly 24-hour, menstrual cycle, and annual rhythms, impact the pharmacokinetics and pharmacodynamics of drugs as a function of their timing. Chronopharmacokinetics is the study of the absorption, distribution, metabolism, and elimination of medicines according to the time of day, menstrual cycle, or year. In addition to applying chronobiology to the study of drugs used in women, new technologies were addressed from computer modeling, pharmacogenetics (genetics of the response to drugs), and in vivo drug metabolism studies.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"617-29"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biologic and molecular mechanisms for sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics: Part I.","authors":"Marietta Anthony, Mary J Berg","doi":"10.1089/152460902760360559","DOIUrl":"10.1089/152460902760360559","url":null,"abstract":"<p><p>There are pharmacological differences between women and men that have important clinical consequences. For several drugs, there is a higher incidence in women of drug-induced QT prolongation and a potentially fatal arrhythmia, torsades de pointes. This may be a reflection of the longer baseline QT interval in women. A difference in cardiovascular disease between women and men is that women have a higher mortality rate after myocardial infarction (MI). Women also have a higher rate of hemorrhagic stroke after receiving thrombolytic therapy for an MI. Differences in effectiveness of analgesics have been demonstrated, with kappa opioids providing pain relief for women but not men. Drugs may have different pharmacokinetics in women and men because of differences in phase I and phase II enzymes that metabolize drugs. Conflicting results about biological sex differences have been reported for the major drug metabolizing enzyme, cytochrome P450 3A4 (3A4) and may be related to a role for P-glycoprotein, a cell membrane transporter, reported as two times higher in male livers than those of females. It has been reported that boys need a higher dose of 6-mercaptopurine, which is metabolized by thiopurine methyltransferase (TPMT). TPMT is reported to be 14% higher in male human liver biopsies than those from females. Verapamil, a drug for angina and hypertension, has different clearance and side effects in men and women. Ethnic/racial variations have also been demonstrated with the drug metabolizing enzymes, CYP2C9, 2C19, and 2D6.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"601-15"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ovarian autoimmune disease and ovarian autoantibodies.","authors":"Judith Luborsky","doi":"10.1089/152460902760360540","DOIUrl":"https://doi.org/10.1089/152460902760360540","url":null,"abstract":"<p><p>Detection of specific autoantibodies remains the most practical clinical and research marker of autoimmune disease. The lack of consensus on ovary specific antibodies as a marker for ovarian autoimmunity has clinical and research consequences. The objective of this review is to summarize the evidence for ovarian autoimmunity and the detection of ovary specific autoantibodies in humans. Evidence favors the presence of an autoimmune disease of the ovary. Ovarian autoantibodies are associated primarily with premature ovarian failure (POF) and unexplained infertility. Variations in detection of ovarian autoantibodies are likely to be due to study design elements such as antibody test format, antigen preparation, and criteria for study and comparison groups. In addition, multiple targets appear to be involved in ovarian autoimmunity including ovarian cellular elements and oocyte related antigens. Many studies only assess one target antigen, leaving individuals with ovarian autoimmunity unidentified. The next most significant advance in characterizing ovarian autoimmunity will be definitive identification of the specific antigens and development of standardized tests based on use of specific antigens.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"585-99"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toward optimal health: the experts discuss polycystic ovary syndrome.","authors":"Andrea Dunaif, Rogerio A Lobo","doi":"10.1089/152460902760360531","DOIUrl":"https://doi.org/10.1089/152460902760360531","url":null,"abstract":"","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"579-84"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22080810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The personal costs and convenience of screening mammography.","authors":"Lisa Gale Suter, Connie Y Nakano, Joann G Elmore","doi":"10.1089/152460902760360603","DOIUrl":"https://doi.org/10.1089/152460902760360603","url":null,"abstract":"<p><strong>Background: </strong>Few studies have examined the impact of women's personal costs on obtaining a screening mammogram in the United States.</p><p><strong>Methods: </strong>All women obtaining screening mammograms at nine Connecticut mammography facilities during a 2-week study period were asked to complete a questionnaire. Facilities included urban and rural fixed sites and mobile sites. The survey included questions about insurance coverage, mammogram payment, and personal costs in terms of transportation, family care, parking, and lost work time from the women's perspective.</p><p><strong>Results: </strong>The response rate was 62% (731 of 1189). Thirty-two percent of respondents incurred some type of personal cost, including lost work time, family care, and parking. Women incurring personal costs were more likely than those without personal costs to attend an urban facility (46% vs. 23%, p < 0.01) and be under the age of 50 (40% vs. 26%, p < 0.01). Overall, 61% of women listed convenience and 17% listed cost as a reason for choosing a mammography facility; 23% reported that cost might prevent them from obtaining a future mammogram.</p><p><strong>Conclusions: </strong>One third of women obtaining mammograms may be incurring personal costs. These personal costs should be considered in future cost-effectiveness analyses.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"667-72"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enrique F Schisterman, Amy M Gallagher, C Noel Bairey Merz, Brian W Whitcomb, David Faraggi, Kristen B Moysich, Howard Lewin
{"title":"The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography.","authors":"Enrique F Schisterman, Amy M Gallagher, C Noel Bairey Merz, Brian W Whitcomb, David Faraggi, Kristen B Moysich, Howard Lewin","doi":"10.1089/152460902760360577","DOIUrl":"https://doi.org/10.1089/152460902760360577","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have shown that hormone replacement therapy (HRT) is associated with lower coronary heart disease (CHD), and animal studies demonstrate potent antiatherosclerotic estrogen effects. Paradoxically, recent clinical trials have not demonstrated a protective effect. This paradox may be explained by a healthy woman effect bias. Women using HRT have improved health outcomes unrelated to underlying atherosclerotic burden. Examination of the association between coronary calcium (CC), a marker of atherosclerotic plaque burden, and the use of HRT in postmenopausal women may help address this paradox.</p><p><strong>Methods: </strong>The study population comprised 641 asymptomatic postmenopausal women, 425 (66%) of whom were taking HRT. Data obtained from a self-administered questionnaire and blood samples were analyzed. Electron beam tomography (EBT) for CC was performed on each subject. Analysis of variance (ANOVA) was used to evaluate adjusted means.</p><p><strong>Results: </strong>Independent t tests found that age, low-density lipoproteins (LDL), high-density lipoproteins (HDL), body mass index (BMI), vitamin use, coronary calcium score (CCS), coronary calcified volume (CCV), and the number of coronary calcium lesions (CCL) were significantly different between the HRT group and the non-HRT group. However, after controlling for potential confounders, no significant differences were observed in CCS, CCV, or the number of CCL between the HRT and non-HRT groups. Stratifying by BMI shows that obese/overweight women taking HRT have lower adjusted CCS and fewer CCL than the obese/overweight women not taking HRT.</p><p><strong>Conclusions: </strong>These findings demonstrate no association between HRT use and CCS, CCV, and CCL after adjusting for measurable confounders in postmenopausal women. Our failure to demonstrate an independent association between HRT use and a marker of atherosclerotic plaque burden suggests that a healthy woman effect may explain the beneficial association between HRT use and CHD in observational studies.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"631-8"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maintaining fairness: who gets funded at NIH, and is the process fair?","authors":"Florence P Haseltine","doi":"10.1089/152460902760360504","DOIUrl":"https://doi.org/10.1089/152460902760360504","url":null,"abstract":"","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"569-70"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22080808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathleen Ell, Betsy Vourlekis, Laila Muderspach, Jan Nissly, Deborah Padgett, Diana Pineda, Olga Sarabia, Pey-Jiuan Lee
{"title":"Abnormal cervical screen follow-up among low-income Latinas: Project SAFe.","authors":"Kathleen Ell, Betsy Vourlekis, Laila Muderspach, Jan Nissly, Deborah Padgett, Diana Pineda, Olga Sarabia, Pey-Jiuan Lee","doi":"10.1089/152460902760360586","DOIUrl":"https://doi.org/10.1089/152460902760360586","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer incidence and mortality rates are dramatically higher among low-income women than in the general population, in part due to poor adherence to recommended diagnostic follow-up after an index Pap test. This report describes a pilot study of the Screening Adherence Follow-Up Program (SAFe), an individualized, structured case management program designed to assess for and intervene in response to a variety of potential personal and systems barriers to follow-up adherence. Interventions included health education, counseling, and systems navigation.</p><p><strong>Methods: </strong>A clinical decision-making algorithm was used to determine service intensity and level of intervention. Services were provided to 196 low-income women, predominantly Latinas, who had either a low-grade or high-grade squamous intraepithelial lesion (LGSIL or HGSIL) abnormal Pap result. Adherence rates to at least one follow-up appointment after enrollment and baseline intervention were 83% following LGSIL and 93% for HGSIL.</p><p><strong>Results: </strong>Over 1 year post-enrollment, 41% of women with LGSIL were fully adherent, with 42% partially adherent; 61% of women with HGSIL were fully adherent, with 32% partially adherent. In a comparison group of 369 nonenrollees (women who refused participation or could not be located for consent), adherence rates were 58% for LGSIL and 67% for HGSIL. A survey among a random sample of women served indicated that 93% were \"mostly\" or \"very\" satisfied, overall, with SAFe services.</p><p><strong>Conclusions: </strong>The intervention team--a peer counselor and a master's degreed social worker--addressed multiple psychosocial and systems navigation problems to reduce potential barriers to adherence, including knowledge, attitudinal, psychosocial, psychological distress, systems communication, and resource access problems. SAFe appears highly acceptable to women and may significantly enhance medical care management following an abnormal cervical screen for a carefully targeted group of women at risk for suboptimal follow-up adherence.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"639-51"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Entertainment outreach for women's health at CDC.","authors":"Kathryn E Wilson, Vicki H Beck","doi":"10.1089/152460902760360522","DOIUrl":"https://doi.org/10.1089/152460902760360522","url":null,"abstract":"","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"575-8"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22080809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarina Hamberg, Gunilla Risberg, Eva E Johansson, Göran Westman
{"title":"Gender bias in physicians' management of neck pain: a study of the answers in a Swedish national examination.","authors":"Katarina Hamberg, Gunilla Risberg, Eva E Johansson, Göran Westman","doi":"10.1089/152460902760360595","DOIUrl":"https://doi.org/10.1089/152460902760360595","url":null,"abstract":"<p><strong>Background: </strong>Research has raised concerns about gender bias in medicine; that is, are women and men being treated differently because of gender stereotyped attitudes among physicians? We investigated gender differences in the diagnosis and management of neck pain as proposed in a written test. The design eliminated differences related to communication and patient behavior.</p><p><strong>Methods: </strong>In a national examination for Swedish interns, using modified essay questions, the examinees were allocated to suggest management of neck pain in either a male or a female bus driver with a tense family situation. The case description was identical with the exception of patient gender. The open answers were coded for analysis. Two hundred thirty-nine interns (41% women) participated. Chi-square-tests were used to measure differences in proportions, and t test was used to evaluate differences in means.</p><p><strong>Results: </strong>In certain areas, significant gender differences were detected. Proposals of nonspecific somatic diagnoses, psychosocial questions, drug prescriptions, and the expressed need of diagnostic support from a physiotherapist and an orthopedist were more common with females. Laboratory tests were requested more often in males. Both male and female physicians contributed to the gender differences. When assessing the impact of the patient-doctor relationship for health outcome, male physicians underlined the importance of patient compliance foremost in female patients, and female physicians did the opposite.</p><p><strong>Conclusions: </strong>The results suggest that physicians' gendered expectations are involved in creating gender differences in medicine. The inclusion of gender theory and discussions about gender attitudes into medical school curricula is recommended to bring about awareness of the problem.</p>","PeriodicalId":80044,"journal":{"name":"Journal of women's health & gender-based medicine","volume":"11 7","pages":"653-66"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152460902760360595","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22081339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}