To model the effectiveness that can be obtained if levonorgestrel-only emergency contraception (EC) acts only through disrupting ovulation, in relation to other effects that may occur before or after fertilization and accounting for delays in administration. We modeled follicular growth as a function of follicular size, using known day-specific probabilities of conception and known disruption of ovulation by levonorgestrel-only EC, to estimate the expected effectiveness of EC. Combined data from multiple clinical studies. PATIENT(S): Simulation models. INTERVENTION(S): Disruption of ovulation. MAIN OUTCOME MEASURE(S): Effectiveness in the form of proportion of pregnancies prevented. RESULT(S): With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay). CONCLUSION(S): The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects. Additional data with follicular ultrasound and precise measures of delay between intercourse and EC administration would yield greater insight into effectiveness and mechanisms of action.
Fertility AwarenessSymptothermal MethodPerfect and Imperfect Use RatesProspective Cohort Studies
The efficacy of fertility awareness based (FAB) methods of family planning is critically reviewed. The objective was to investigate the efficacy and the acceptability of the symptothermal method (STM), an FAB method that uses two indicators of fertility, temperature and cervical secretions observation. This paper will recommend a more suitable approach to measure the efficacy. Since 1985, an ongoing prospective observational longitudinal cohort study has been conducted in Germany. Women are asked to submit their menstrual cycle charts that record daily basal body temperature, cervical secretion observations and sexual behaviour. A cohort of 900 women contributed 17,638 cycles that met the inclusion criteria for the effectiveness study. The overall rates of unintended pregnancies and dropout rates have been estimated with survival curves according to the Kaplan-Meier method. In order to estimate the true method effectiveness, the pregnancy rates have been calculated in relation to sexual behaviour using the 'perfect/imperfect-use' model of Trussell and Grummer-Strawn. After 13 cycles, 1.8 per 100 women of the cohort experienced an unintended pregnancy; 9.2 per 100 women dropped out because of dissatisfaction with the method; the pregnancy rate was 0.6 per 100 women and per 13 cycles when there was no unprotected intercourse in the fertile time. The STM is a highly effective family planning method, provided the appropriate guidelines are consistently adhered to.
Kagami M et al., 2007·Journal of Assisted Reproduction and Genetics
The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART.
Fertility AwarenessFecundability EstimationTime to Pregnancy StudiesIntercourse Pattern Effects
Time to pregnancy, typically defined as the number of menstrual cycles required to achieve a clinical pregnancy, is widely used as a measure of couple fecundity in epidemiologic studies. Time to pregnancy studies seldom utilize detailed data on the timing and frequency of sexual intercourse and the timing of ovulation. However, the simulated models in this paper illustrate that intercourse behavior can have a large impact on time to pregnancy and, likewise, on fecundability ratios, especially under conditions of low intercourse frequency or low fecundity. Because intercourse patterns in the menstrual cycles may vary substantially among groups, it is important to consider the effects of sexual behavior. Where relevant and feasible, an assessment should be made of the timing and frequency of intercourse relative to ovulation. Day-specific probabilities of pregnancy can be used to account for the effects of intercourse patterns. Depending on the research hypothesis, intercourse patterns may be considered as a potential confounder, mediator, or outcome.
Bone HealthAbsolute Risk MethodsPrevalence and ScreeningProspective Cohort Study
The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk.
Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.
Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation. Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined. Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data. These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.
Rotem C et al., 2007·Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms. A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography. The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group. Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.
Depression and osteoporotic fractures are common ailments among elderly persons. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of depression in this population, and the association between daily SSRI use and fragility fractures is unclear. Our objective was to examine the effect of daily SSRI use on the risk of incident clinical fragility fracture. A population-based, randomly selected, prospective cohort study of 5008 community-dwelling adults 50 years and older, followed up over 5 years for incident fractures. Clinical fragility fractures were classified as minimal trauma fractures that were clinically reported and radiographically confirmed. The risk of fragility fracture associated with daily SSRI use was determined while controlling for relevant covariates. Daily SSRI use was reported by 137 subjects. After adjustment for many potential covariates, daily SSRI use was associated with substantially increased risk of incident clinical fragility fracture (hazard rate, 2.1; 95% confidence interval, 1.3-3.4). Daily SSRI use was also associated with increased odds of falling (odds ratio, 2.2; 95% confidence interval, 1.4-3.5), lower bone mineral density at the hip, and a trend toward lower bone mineral density at the spine. These effects were dose dependent and were similar for those who reported taking SSRIs at baseline and at 5 years' follow-up. Daily SSRI use in adults 50 years and older remained associated with a 2-fold increased risk of clinical fragility fracture after adjustment for potential covariates. Depression and fragility fractures are common in this age group, and the elevated risk attributed to daily SSRI use may have important public health consequences.
Contraception/ComparisonCancer RiskHormonal Risk FactorsCase-Control Study
To estimate breast cancer risk associated with short-term (<6 months) oral contraceptive use, and explore variation in estimates by use characteristics and medical, menstrual, and reproductive history. We analyzed data from the Women's Contraceptive and Reproductive Experiences Study. Case subjects were white women and black women, 35-64 years old, diagnosed with invasive breast cancer in July 1994-April 1998. Control subjects identified by random-digit dialing were matched to case subjects by age, race, and study site. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, short-term oral contraceptive use was not associated with breast cancer risk (OR = 1.0; 95% CI = 0.8-1.1). However, significant interaction between short-term use and menopausal status led to an observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI = 1.0-1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6-1.0) associated with short-term use. The association was more pronounced in women with non-contraceptive reasons for use and underlying risk factors for breast cancer. These associations may result from underlying characteristics of users or unmeasured factors influencing duration of use and breast cancer risk.
Contraception/ComparisonInfectious Disease RiskHIV AcquisitionProspective Cohort Study
Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.
Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The inflammatory reactions within the male genital tract are inevitably connected with oxidative stress. Growing evidence indicates that imbalance between prooxidative and anti-oxidative substances in semen leads to metabolic and functional disorders of male germ cells and may be a primary cause of some types of infertility. The infectious factor and local tissue damage can lead to the infiltration of leukocytes to the inflammatory site. This is in an obvious way connected to the production and release of large amounts of reactive oxygen species (ROS), which trigger immune responses directed against the infectious agent, and the simultaneous secretion of numerous biological substances, thereby escalating the inflammation. Some of these factors are proteases and proinflammatory cytokines. Extended exposure of spermatozoa to ROS may lead to the peroxidation of sperm membrane lipids. Many studies point to the combined activities of inflammatory mediators in exerting toxic effects on spermatozoa. The local influences of biologically active substances released by activated leukocytes in the course of the inflammatory response and the mutual interactions of various factors (bacteria, leukocytes, proinflammatory cytokines) at the site represent a complex puzzle.
Oral contraceptives (OCs) remain among the most effective reversible methods of birth control available today, providing almost 100% effectiveness with an impressively high margin of safety and other important health benefits. However, concerns have been raised about the role that the hormones in OCs might play in the pathogenesis of cervical cancer. Evidence shows that long-term use of OCs (five or more years) may be associated with an increased risk of cancer of the cervix. The mechanism of increased risk of cervical cancer in OCs users has long been debated, and remains uncertain. Our hypothesis is that scanty, thick, and highly viscous cervical mucus obtained in OCs users intimately involved in the pathogenesis of cervical cancer. Possibly, this architecture of cervical mucus may modulate and prolong the effect of carcinogenic agents, which have been carried by coitus and stored in posterior vaginal fornix, on squamocolumnar junction of cervix by not permitting them to be removed because of its highly viscous pattern. The role of cervical mucus changes by means of specific mucin protein changes on the pathophysiology of cervical cancer in OCs users should be investigated.
Perimenopause/MenopauseParticipatory MethodsCommunity-Based ResearchParticipatory Research
No AccessOther Health Study28 Jun 2021Walking the TalkReimagining Primary Health Care After COVID-19Authors/Editors: //doi.org/10.1596/35842SectionsAboutPDF (22.7 MB) ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked The world has waited long enough for high-performing primary health care (PHC). It's time to deliver. Forty years ago, leaders embraced the promise of health for all through PHC. That vision has inspired generations. But for nearly half a century, countries have struggled to walk the talk on PHC. We have not built health systems anchored in strong PHC where they were needed most. Today, COVID-19 (coronavirus) has brought the reckoning for that shared failure—but also the chance to do the job right at last. The pandemic has shown policy makers and ordinary citizens why health systems matter and what happens when they fail. By doing so, it has also created a oncein-a-generation chance for structural health-system change. Bold reforms now can prepare health systems for future crises and bring goals like universal health coverage (UHC) within reach. PHC holds the key to these transformations. But to fulfill that promise, the walk has to finally match the talk. This report charts an agenda toward reimagined, fit-for-purpose PHC. It asks three questions about health-systems "Why?", "What?", and "How?" Since PHC has been around for decades, why write a thick report about it now? The answer is that the characteristics of high-performing PHC are exactly those that are most critical for managing the pressures coming to bear on health systems in the post-COVID world. The challenges include future infectious outbreaks and other emergent threats, but also long-term structural trends that are reshaping the environments in which systems operate in non-crisis times. This report highlights three sets of megatrends that will increasingly affect health demographic and epidemiological shifts; changes in technology; and citizens' evolving expectations for health care. Previous bookNext book FiguresreferencesRecommendeddetails June 2021 Copyright & Permissions Related TopicsHealth Nutrition and Population KeywordsCORONAVIRUSCOVID-19ACCOUNTABILITYHEALTH CARE REFORM PDF DownloadLoading ...
Plasma 25-hydroxyvitamin D was measured in 40 healthy, mostly Black, mother-infant pairs. Although a majority of mothers received a daily prenatal multivitamin, vitamin D deficiency (<30 nmol/L), was found in 50% of mothers and 65% of their newborn infants, with a positive correlation between maternal and infant plasma 25-hydroxyvitamin D concentrations. Maternal vitamin D deficiency may represent an important risk factor for the development of rickets in children.
Chavarro JE et al., 2007·The American Journal of Clinical Nutrition
Pharmacologic activation of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) improves ovulatory function in women with polycystic ovary syndrome, and specific dietary fatty acids can affect PPAR-gamma activity. The objective of the study was to assess whether the intakes of total fat, cholesterol, and major types of fatty acids affect the risk of ovulatory infertility. We conducted a prospective cohort study of 18 555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999. Diet was assessed twice during follow-up by using a food-frequency questionnaire. During follow-up, 438 incidents of ovulatory infertility were reported. In logistic regression analyses, intakes of total fat, cholesterol, and most types of fatty acids were not related to ovulatory infertility. Each 2% increase in the intake of energy from trans unsaturated fats, as opposed to that from carbohydrates, was associated with a 73% greater risk of ovulatory infertility after adjustment for known and suspected risk factors for this condition [relative risk (RR) = 1.73; 95% CI: 1.09, 2.73]. Obtaining 2% of energy intake from trans fats rather than from n-6 polyunsaturated fats was associated with a similar increase in the risk of ovulatory infertility (RR = 1.79; 95% CI: 1.11, 2.89). In addition, obtaining 2% of energy from trans fats rather than from monounsaturated fats was associated with a more than doubled risk of ovulatory infertility (RR = 2.31; 95% CI: 1.09, 4.87).Conclusiontrans Unsaturated fats may increase the risk of ovulatory infertility when consumed instead of carbohydrates or unsaturated fats commonly found in nonhydrogenated vegetable oils.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2006. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Andersen AN et al., 2007·Human reproduction (Oxford, England)
30. Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE. Andersen AN(1), Goossens V, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG. (1)Central Office, European Society of Human Reproduction and Embryology, Meerstraat 60, B-1852 Grimbergen, Belgium. bruno.vandeneede@eshre.com European results of assisted reproductive techniques (ARTs) from treatments initiated during 2003 are presented in this seventh report. Data were mainly collected from already existing national registers. From 28 countries, 725 clinics reported 365 103 IVF 132 932, ICSI 162 149, frozen embryo replacement (FER) 60 412, oocyte donation (OD) 7548, PGD/PGS 1956 and IVM 109. Overall, this represents a 13% increase since 2002. For the third time, results on European data on intrauterine inseminations (IUIs) were reported from 19 countries. A total of 99 577 cycles (IUI-H, 82 834; IUI-D, 16 743) were included. In those 15 countries where all clinics reported to the register, a total of 284 765 cycles were performed in a population of 278.7 million, corresponding to 1022 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.1 and 29.6%, respectively. For ICSI, the corresponding rates were 26.5 and 28.7%. After IUI-H, the clinical pregnancy rate was 12.2% in women below 40 years and 8.8% in women > or =40 years. After IVF and ICSI, the distribution of transfer of one, two, three and four or more embryos was 15.7, 55.9, 24.9 and 3.5%, respectively. Compared to the year 2002, fewer embryos were transferred, but huge differences still exist between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 76.7, 22.0 and 1.1%, respectively. This gives a total multiple delivery rate of 23.1% compared with 24.5% in 2002. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 4.4% between countries. After IUI-H in women below 40 years of age, 11.4% were twin and 2.2% triplet gestations.
Contraception/ComparisonHIV RiskSafety OutcomesProspective Cohort Study
Many women using hormonal contraceptives are also at risk of sexually transmitted HIV infection, but data are mixed on whether hormonal contraception increases women's risk of HIV. We investigated associations between HIV incidence and use of combined oral contraceptives (COC), norethindrone enanthate (NET-EN) or depot medroxyprogesterone acetate (DMPA) in a cohort of South African women. Participants were 4200 HIV-negative women aged 35-49 years enrolled into a cervical cancer screening trial. At enrollment, women were tested for sexually transmitted infections and reported on their sexual behaviour and contraceptive use. During the 24 months of follow-up, women reported on their sexual behaviours and contraceptive use and underwent repeat HIV testing. During the 5010 person-years of follow-up, 111 incident HIV infections were observed (HIV incidence, 2.2 infections/100 person-years). At enrollment, 21% of women reported using hormonal contraception, primarily DMPA (14% of all women) or NET-EN (5%). After adjusting for sexual risk behaviours and sexually transmitted infections, the incidence of HIV was similar among women using COC, NET-EN or DMPA compared with women not using any hormonal method [incidence rate ratios and 95% confidence intervals, 0.65, 0.16-2.66; 0.79, 0.31-2.02 and 0.96, 0.58-1.59, respectively]. There was also no association between increased duration of DMPA use and HIV incidence (P-value for trend, 0.51). These findings contribute to the evidence from general population cohorts of women that hormonal contraceptive use is not associated with increased risk of HIV acquisition. Nonetheless, family planning services are an important venue for HIV prevention activities.
Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin - owing to its metabolic, endocrine, vascular and anti-inflammatory effects - may reduce the incidence of first-trimester abortion in PCOS women. A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000-2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group. Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11-0.42). Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.
Bone HealthFSH and Bone ResorptionFSH PhysiologyEstrogen Deficiency Paradigm
For many years, osteoporosis in women was equated with estrogen deficiency. The recent articles by Zaidi and colleagues offer a new challenge to the estrogen-deficiency-osteoporosis hypothesis by showing that follicle-stimulating hormone (FSH) stimulates osteoclastic bone resorption perhaps through tumor necrosis factor-alpha (TNF-alpha). These authors, however, neglected to mention bone abnormalities and high testosterone levels that were previously shown in FSH-receptor knockout and other modified mice. It is also possible that they have overemphasized potential relationships of these new data with human bone loss. Despite these fascinating data, the paradigm of FSH causing hypogonadal bone loss is not yet ready to displace the estrogen-deficiency-osteoporosis paradigm, although that model already faces considerable challenge.
Song GJ et al., 2006·International journal of andrology
Ascorbic acid has recently been reported to protect sperm DNA from the damage induced by exogenous oxidative stress in vitro. But, there is no report on seminal ascorbic acid and sperm DNA fragmentation in infertile men. In this study, we asked whether sperm DNA damage correlates with seminal ascorbic acid levels. Sperm DNA fragmentation index (DFI) was analysed in 75 men by flow cytometry after acridine orange staining. We also measured the levels of seminal plasma ascorbic acid and total antioxidant capacity. Abnormal sperm DNA integrity (DFI >or= 30%) was observed in 12% of the patients with normal semen parameters and in 52% of the patients with abnormal semen parameters. There were significant correlations between the level of DFI and conventional semen parameters including sperm count, motility and morphology (r = -0.29, -0.55 and -0.53 respectively; p < 0.05). Seminal ascorbic acid level was significantly lower in the patients with leucospermia than the patient with normal semen parameters. Interestingly, a significantly greater percentage of men with abnormal DFI were observed in the patients with low levels of seminal ascorbic acid compared with those with normal or high levels of ascorbic acid (59% vs. 33%, p < 0.05). Men with insufficient seminal ascorbic acid frequently have sperm DNA damage.
Routine bone mineral densitometry (BMD) screening has been recommended for women aged >or=65 yr (Osteoporosis Canada [OC], International Society for Clinical Densitometry [ISCD], Canadian and United States Task Forces on Preventative Healthcare, and National Osteoporosis Foundation) and for men >or=65 yr (OC) or >or=70 yr (ISCD). We estimated the number of older Canadians needed to screen (NNS) by BMD to detect an undiagnosed case of osteoporosis, using prospective, multicenter, population-based data from the Canadian Multicentre Osteoporosis Study (CaMos). We included participants aged >or=65 yr with baseline dual-energy X-ray absorptiometry (DXA) BMDs at the femoral neck and lumbar spine (L1-L4). Osteoporosis was defined by a T-score or=65 yr. The percentage prevalence and 95% confidence intervals were determined. In individuals aged >or=65 yr, the prevalence of osteoporosis was 25.6% in women (95% confidence interval, 24.0%, 27.3%) and 8.9% in men (7.3%, 10.8%). In 652 men aged >or=70 yr, the prevalence of osteoporosis was 11.3% (9.1%, 14.0%). Of the participants with BMD-defined osteoporosis, 76.6% of woman aged >or=65 yr (73.2%, 79.6%; 516 of 674 women), 93.4% of men aged >or=65 yr (86.4%, 96.9%; 85 of 91), and 93.2% of men >or=70 yr (84.9%, 97.0%; 68 of 73) were not aware of it. Thus, the minimum NNS by BMD testing to detect one previously undiagnosed case 6 women aged >or=65 yr, 13 men aged >or=65 yr, and 10 men aged >or=70 yr.
Body LiteracyMenstrual Cycle as Vital SignAdolescent Menstrual PatternsMenstrual Assessment
Young patients and their parents often are unsure about what represents normal menstrual patterns, and clinicians also may be unsure about normal ranges for menstrual cycle length and amount and duration of flow through adolescence. It is important to be able to educate young patients and their parents regarding what to expect of a first period and about the range for normal cycle length of subsequent menses. It is equally important for clinicians to have an understanding of bleeding patterns in girls and adolescents, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate young patients' conditions appropriately. Using the menstrual cycle as an additional vital sign adds a powerful tool to the assessment of normal development and the exclusion of pathological conditions.
To investigate the reasons women experience delays in the diagnosis of endometriosis and the impact of this. A qualitative interview-based study of 32 women, 28 of whom were subsequently diagnosed with endometriosis. Southeast England. PATIENT(S): Women attending a pelvic pain clinic. INTERVENTION(S): Semistructured interviews. MAIN OUTCOME MEASURE(S): Women's reported experiences of being diagnosed with endometriosis. RESULT(S): Delays in the diagnosis of endometriosis occur at an individual patient level and a medical level, as both women and family doctors normalize symptoms, symptoms are suppressed through hormones, and nondiscriminatory investigations are relied upon. Women benefited from a diagnosis, because it provided a language in which to discuss their condition, offered possible management strategies to control symptoms, and provided reassurance that symptoms were not due to cancer. Diagnosis also sanctioned women's access to social support and legitimized absences from social and work obligations. CONCLUSION(S): Although recent guidelines for the management of chronic pelvic pain suggest that diagnostic laparoscopy may be considered a secondary investigation after the failure of therapeutic interventions, the present study highlights the importance of an early diagnosis for women who suffer at physical, emotional, and social levels when they remain undiagnosed.
SurgerySalpingectomy for HydrosalpinxIVF OptimizationSurgical Recommendations
Clinically a couple is considered to be infertile after at least one year without contraception and without pregnancy. There was scant knowledge about the prevalences of infertility, involuntary childlessness and the seeking of fertility treatment and only few longitudinal studies about the psychosocial consequences of infertility and its treatment. This thesis is about the epidemiological aspects of infertility; the conceptualization and measurement of important psychosocial aspects of infertility; and a medical sociological analysis of the associations between these psychosocial variables among Danish women and men in fertility treatment. The thesis is based on nine papers. (i) to review critically, population based studies of infertility and medical care seeking in industrialised countries. Further, to examine these prevalences and subsequent motherhood among women in former assisted reproduction in a Danish population. (ii) To develop measures of psychosocial fertility problem stress, marital benefit, communication, coping strategies, attitudes to and evaluation of fertility treatment. (iii) To examine these phenomena and to analyse their interrelations among Danish women and men in fertility treatment. The thesis is based (i) The Women and Health Survey, a cross-sectional population-based study among 15-44 year old women (n=907, 25-44 year old) in Copenhagen County, 1989. (ii) The Psychosocial Infertility Interview Study, a qualitative interview study among 16 couples (n=2 participants) infertility treatment at The Fertility Clinic, Herlev University Hospital,1992. (iii) The Infertility Cohort, a longitudinal cohort study consecutively including all couples (n=250 participants) beginning anew fertility treatment period at one of four public (Braedstrup, Herlev, Odense, Rigshospitalet) and one private fertility clinic (Trianglen),2000-2002. (iv) The Communication and Stress Management Training Programme, an intervention study among couples(n=74 participants) in fertility treatment at The Fertility Clinic, The Juliane Marie Centre, Rigshospitalet, 2001-2003. Included is also a literature review of population-based infertility studies from industrialised countries. Data from (iii) and (iv) are studies from The Copenhagen Multi-centre Psychosocial Infertility (COMPI) Research Programme (www.compipro.dk). Epidemiological and demographic studies investigating the prevalences of infertility differed in how they defined the numerator (the infertile participants) and the denominator (the population at risk). It was important to calculate reliable estimates of the infertility prevalence by including only women who had tried to have at least one child in the population at risk, as a notable proportion of women in the fertile ages had not (yet) attempted to become a mother. The lifetime prevalence of infertility in the representative population-based study was 26.4%. In the age group 35 to 44 years 5.8% were primarily involuntarily in fecund (involuntarily childless). Even in a country with access to fertility treatment in a public health-care system without self-payment lower education was a predictor of lower treatment seeking. In the cohort study (2000-2002)of couples starting a new period of assisted reproduction treatment 62.6% reported a treatment-related pregnancy at the one-year follow-up. In total 32.4% reported a treatment-related delivery. In total 24.2% reported a current continuing pregnancy and spontaneous pregnancies accounted for 2.7% of these. We developed measures of fertility problem stress, marital benefit(that infertility has brought the partners closer together and strengthened their marriage), partner communication, infertility related communication, coping strategies, attitudes to fertility treatment and evaluation of care. The medical sociological analyses showed that the variables of psychosocial consequences of infertility and treatment are interwoven with each others in a complex pattern, a pattern that both differed and was similar when comparing women and men. The infertility-related communication strategy (secrecy, formal, open-minded)identified in the qualitative interviews was later confirmed in the COMPI Infertility Cohort. Using the formal strategy and not talking about the emotional aspects of infertility and its treatment suggested high fertility problem stress. The coping strategies studied showed significant social differences and active-avoidance coping was a significant predictor of high fertility problem stress. A positive effect of infertility on the marriage, marital benefit was common. Men using the secrecy communication strategy had increased risk of low marital benefit. Difficult partner communication was a significant predictor of high fertility problem stress and among men, of low marital benefit. The intervention study showed that it was possible for the participants to change their communication with partner and other people close to them and that participants achieved an increased awareness of what, how much and when to discuss with others. High fertility problem stress and high marital benefit were associated with high importance ratings of patient-centred care and intentions to use professional psychosocial services. Among women, high fertility problem stress was a predictor of lower satisfaction ratings with fertility treatment. High marital benefit was a predictor of high satisfaction ratings of both medical and patient-centred care. In conclusion, infertility is a common experience among couples attempting to become parents. Assisted reproduction in the public health-care system in Denmark has high success rates, i.e. pregnancies,deliveries and high patient satisfaction. A large minority of people in fertility treatment experience high fertility problem stress,and some use communication and coping strategies that predicts high stress. Developing and evaluating different psychosocial interventions are necessary to offer the psychosocial support needed for this minority of fertility patients.
Kariv R et al., 2006·Digestive Diseases and Sciences
Preclinical studies have shown that a very low dose of naltreoxone hydrochloride (NTX), an opiate antagonist, can block excitatory opioid receptors without affecting inhibitory opioid receptors, resulting in analgesic potency without side effects. The present study assessed the efficacy and safety of PTI-901 (low-dose NTX) treatment in Irritable bowel syndrome (IBS) patients. Forty-two IBS patients participated in an open-label study. Participants received 0.5 mg PTI-901/day for 4 weeks and were evaluated during baseline, during treatment, and at 4-week follow-up. Patients recorded degree of abdominal pain, stool urgency, consistency, and frequency. Primary outcomes were number of pain-free days and overall symptom relief, evaluated by a global assessment score. Data were analyzed per protocol. Global assessment improved in 76% of 42 patients. During treatment, the mean weekly number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 (P=0.011). There were no significant adverse reactions. PTI-901 improves pain and overall feeling, and is well tolerated by IBS patients. A large, randomized, double-blind, placebo-controlled study is justified.
Hauser R et al., 2006·Epidemiology (Cambridge, Mass.)
Phthalates are multifunctional chemicals used in a variety of consumer, medical, and personal care products. Previously, we reported dose-response associations of decreased semen quality with urinary concentrations of monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study extends our work in a larger sample of men and includes measurements of di(2-ethylhexyl) phthalate (DEHP) oxidative metabolites. Between January 2000 and May 2004, we recruited 463 male partners of subfertile couples who presented for semen analysis to the Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values for sperm concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg Kruger Strict criteria for morphology (<4% normal). The comparison group was men with all 3 semen parameters above the reference values. In a single spot urine sample from each man, phthalate metabolites were measured using solid-phase extraction coupled to high-performance liquid chromatography isotope-dilution tandem mass spectrometry. There were dose-response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04) and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP metabolites with these semen parameters. The present study confirms previous results on the relationship of altered semen quality with exposure to MBP at general population levels. We did not find associations between semen parameters and 3 DEHP metabolites.
Perimenopause/MenopauseHormonal CharacterizationEstrogen in PerimenopauseWomen's Health Paradigms
Prior et al., 2006·Journal of Reproductive and Infant Psychology
Ordinary women and official statements confuse and conflate perimenopause—the long, complex, life phase of higher and chaotic estrogen levels—with the low and stable estrogen levels of menopause. This paints both perimenopause and menopause with an inaccurate ‘estrogen deficiency’ brush. Menopause is the hormonal, and (except for hot flushes) the experiential opposite of perimenopause. This feminist analysis is from my perspective as physician‐scientist who experienced a perimenopause that was scientifically enlightening, but personally agonizing. Denial of perimenopausal and menopausal differences causes perimenopause to be ‘lost’ (1) we may assume that perimenopause is chronic rather than ending in a largely asymptomatic menopause; (2) societal taboos isolate us, depriving us of solidarity with perimenopause ‘survivors’; (3) we are told we have dropping estrogen levels when our experiences, like pregnancy dreams, tell us the opposite; (4) gynaecology treats heavy flow with estrogen despite higher perimenopausal estrogen levels; (5) feminists ignore hormonal changes and attribute perimenopausal symptoms to (real) stresses of inferior social status and ageing; and (6) many of us thus become menopausal without the unique, self‐actualization experience that perimenopause has the potential to provide. Thus perimenopause—a valuable transition into knowing and standing up for ourselves—becomes lost.
Fertility AwarenessFecundity MeasurementDay-Specific Conception ProbabilitiesFertility Cycle Data Analysis
Mikolajczyk RT et al., 2006·Paediatr Perinat Epidemiol
Approaches to measuring fecundity include the assessment of time to pregnancy and day-specific probabilities of conception (daily fecundities) indexed to a day of ovulation. In this paper, we develop an additional approach of calculating expected pregnancies based on daily fecundities indexed to the last day of the menstrual cycle. Expected pregnancies can thus be calculated while controlling for frequency and timing of coitus. Comparing observed pregnancies with expected pregnancies allows for a standardised comparison of fecundity between studies or groups within studies, and can be used to assess the effects of categorical covariates on the woman or couple level, and also on the cycle level. This can be accomplished in a minimal data set that does not necessarily require hormonal measurement or the explicit identification of ovulation. We demonstrate this approach by examining the effects of age and parity on fecundity in a data set from women monitoring their fertility cycles with the Creighton Model FertilityCare System.
Fertility AwarenessDay-Specific Conception ProbabilitiesBiomarkers and Proxy MeasuresPericonceptional Window Assessment
Conception, as defined by the fertilisation of an ovum by a sperm, marks the beginning of human development. Currently, a biomarker of conception is not available; as conception occurs shortly after ovulation, the latter can be used as a proxy for the time of conception. In the absence of serial ultrasound examinations, ovulation cannot be readily visualised leaving researchers to rely on proxy measures of ovulation that are subject to error. The most commonly charting basal body temperature, monitoring cervical mucus, and measuring urinary metabolites of oestradiol and luteinising hormone. Establishing the timing of the ovulation and the fertile window has practical utility in that it will assist couples in appropriately timing intercourse to achieve or avoid pregnancy. Identifying the likely day of conception is clinically relevant because it has the potential to facilitate more accurate pregnancy dating, thereby reducing the iatrogenic risks associated with uncertain gestation. Using data from prospective studies of couples attempting to conceive, several researchers have developed models for estimating the day-specific probabilities of conception. Elucidating these will allow researchers to more accurately estimate the day of conception, thus spawning research initiatives that will expand our current limited knowledge about the effect of exposures at critical periconceptional windows. While basal body temperature charting and cervical mucus monitoring have been used with success in field-based studies for many years, recent advances in science and technology have made it possible for women to get instant feedback regarding their daily fertility status by monitoring urinary metabolites of reproductive hormones in the privacy of their own homes. Not only are innovations such as luteinising hormone test kits and digital fertility monitors likely to increase study compliance and participation rates, they provide valuable prospective data that can be used in epidemiological research. Although we have made great strides in estimating the timing and length of the fertile window, more work is needed to elucidate the day-specific probabilities of conception using proxy measures of ovulation that are inherently subject to error. Modelling approaches that incorporate the use of multiple markers of ovulation offer great promise to fill these important data gaps.
Contraception/ComparisonBreast Cancer RiskPremenopausal Breast CancerOral Contraceptive Safety
To perform a meta-analysis of case-control studies that addressed whether prior oral contraceptive (OC) use is associated with premenopausal breast cancer. We searched the MEDLINE and PubMed databases and bibliography reviews to identify case-control studies of OCs and premenopausal breast cancer published in or after 1980. Search terms used included breast neoplasms, oral contraceptives, contraceptive agents, and case-control studies. Studies reported in all languages were included. Thirty-four studies were identified that met inclusion criteria. Two reviewers extracted data from original research articles or additional data provided by study authors. We used the DerSimonian-Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs) and the Mantel-Haenszel test to assess association between OC use and cancer. Use of OCs was associated with an increased risk of premenopausal breast cancer in general (OR, 1.19; 95% CI, 1.09-1.29) and across various patterns of OC use. Among studies that provided data on nulliparous and parous women separately, OC use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI, 1.20-1.40) and nulliparous (OR, 1.24; 95% CI, 0.92-1.67) women. Longer duration of use did not substantially alter risk in nulliparous women (OR, 1.29; 95% CI, 0.85-1.96). Among parous women, the association was stronger when OCs were used before first full-term pregnancy (FFTP) (OR, 1.44; 95% CI, 1.28-1.62) than after FFTP (OR, 1.15; 95% CI, 1.06-1.26). The association between OC use and breast cancer risk was greatest for parous women who used OCs 4 or more years before FFTP (OR, 1.52; 95% CI, 1.26-1.82). Use of OCs is associated with an increased risk of premenopausal breast cancer, especially with use before FFTP in parous women.
Fertility AwarenessStandard Days and TwoDay MethodCoital Frequency and TimingBehavioral Outcomes FAB Methods
Fertility awareness-based methods of family planning help women to identify the days of the cycle they should avoid unprotected intercourse to prevent pregnancy. Therefore using fertility awareness-based methods influences the timing of sexual activity, which may affect the nature of the sexual relationship. Data are used from the clinical trials of two fertility awareness-based methods--the Standard Days Method and the TwoDay Method--to determine the frequency and timing of intercourse during the cycle, and the determinants of coital frequency. The mean coital frequency of study participants was similar to that reported by users of other methods. Results suggest that coital frequency increases with consecutive cycles of method use. At the same time the frequency of intercourse during the identified fertile days and during menses decreases. This evidence implies a behavioural change as couples get more experience using their method and communicating about the fertile days. Coital frequency was also influenced by the method used and by the study sites. Potential differences between the methods and sites that may contribute to this effect are discussed.
Bone HealthSupplementation FormsErgocalciferol vs CholecalciferolNarrative Review
Supplemental vitamin D is available in 2 ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D2. The case that vitamin D2 should no longer be considered equivalent to vitamin D3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.
Haile RW et al., 2006·Cancer Epidemiol Biomarkers Prev
Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice. We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years. For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P(trend) = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (OR(trend) per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later. We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue.
Contraception/ComparisonGastrointestinal EffectsEnvironmental Risk FactorsCo-Twin Control Study
Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method. A questionnaire was sent to 317 twin pairs regarding markers of exposures infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups. The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1). The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.
Fertility AwarenessKnowledge Attitude PracticeRhythm MethodDeveloping Countries
Sub-Saharan Africa has one of the highest fertility rates in the world, which is further promoted by the low utilisation of modern contraceptive methods. Yet, many communities claim to have traditional methods of family planning that pre-date the introduction of modern contraceptives, implying that contraception is a culturally acceptable norm. It was therefore postulated that the study population would have a high level of awareness and practice of natural methods of family planning. We aimed to obtain an insight into the extent and correctness of knowledge about natural family planning methods, and its practice as a guide to the general acceptance of contraception as a concept. Pre-tested structured questionnaires were administered to women of childbearing age in households properly numbered for primary healthcare activities. The level of awareness of natural family planning methods was significantly less than awareness for modern methods of contraception. The awareness rate for rhythm method, lactational amenorrhoea method and coitus interruptus was 50.7%, 42.1% and 36.1%, respectively. For all three national family planning methods, there is a steady decline between awareness, correct description of method and utilisation, a difference that was statistically significant in all cases. The sociodemographic factors of the responders had varying influence on utilisation of all three natural family planning methods studied. Rural dwellers practised the lactational amenorrhoea method significantly more often than urban dwellers. Significantly more Muslims than Christians with four children or more practised coitus interruptus or the rhythm method, while the use of lactational amenorrhoea method was significantly increased with the number of living children in both religious groups. There is a relatively low level of awareness of natural family planning methods in the study population, poor utilisation and wrong use of methods. Therefore, improving the correct level of information on natural family planning methods is likely to improve the use of both natural family planning and modern contraceptive methods.
We performed a cross-sectional survey of 357 reproductive-aged women, mostly Hispanic (81.8%), presenting for ambulatory and hospital reproductive care in Phoenix, AZ, about their interest in natural family planning (NFP). Participants completed questionnaires, and responses were analyzed to determine predictors of interest in NFP. Sixty-one percent stated that they were likely or very likely to use NFP to avoid pregnancy, and 50% would use NFP to achieve pregnancy. Of factors studied, Hispanic ethnicity, lower level of acculturation, less education and recent use of condoms or withdrawal were independently associated with interest in using NFP to avoid pregnancy. Younger age and desire for future pregnancy were independently predictive of potential NFP use to achieve pregnancy. This study suggests that Hispanic women find NFP to be an appealing family planning alternative.
Fischer TW et al., 2006·International journal of oncology
Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10(-12)-10(-3) M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor RORalpha by RT-PCR. Melatonin at pharmacological concentrations (10(-3)-10(-7) M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10(-12)-10(-10) M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor RORalpha including its isoform RORalpha4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.
García-Santos G et al., 2006·Journal of pineal research
Low concentrations (nanomolar) of melatonin had been previously shown to inhibit cell proliferation in several cancer cell lines as well as in experimental animal models. Additionally, cell growth inhibition and differentiation of prostate cancer cell lines by high concentrations (micromolar to millimolar) of melatonin have been recently reported. In the present paper, we show the induction of apoptosis by high doses of melatonin in the human neuroblastoma cell line SK-N-MC. We found accumulation of cells in the G2/M cell cycle phase and induction of cellular death, measured as lactate dehydrogenase (LDH) released into the culture medium, under millimolar concentration of melatonin. Apoptosis was evaluated using 4,6-diamidino-2-phenylindole staining, DNA gel electrophoresis, electron microscopy, and annexin V binding. Apoptosis progressed through the classical pathway, which involves caspase-3 activation. Cell death was dose and time-dependent; the lowest effective concentration of melatonin was 100 microm. Treatment with 1 mm melatonin for 6 days induced cell death in 75% of the cells. This novel finding shows that a nontoxic natural indoleamine may be potential therapy for some types of human neuroblastomas.
Hadziomerovic D et al., 2006·Fertility and Sterility
Evaluation of the effects of naltrexone on hyperinsulinemia and hyperandrogenemia in hyperandrogenemic, hyperinsulinemic women. Controlled clinical study. Department of Gynecologic Endocrinology and Reproductive Medicine, Center of Obstetrics and Gynecology, Medical University of Innsbruck, Austria. PATIENT(S): Thirty-nine hyperandrogenemic, hyperinsulinemic women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/d) for >or=3 weeks. MAIN OUTCOME MEASURE(S): Body mass index (BMI), gonadotropin (LH, FSH) and androgen (T, free T, DHEAS) levels, and plasma levels of glucose, insulin, and C-peptide, during a standard 75-g oral glucose tolerance test (OGTT), were determined before and during chronic opiate receptor blockade. RESULT(S): The BMI did not change during therapy. When OGTT was repeated after treatment with naltrexone, glucose levels were not different from those before treatment. Insulin response, however, had dramatically declined. We also observed a significant decrease in the levels of serum androgens. CONCLUSION(S): Hyperinsulinemia associated with hyperandrogenemia can be improved or completely abolished by chronic opiate receptor blockade. This observation suggests that endogenous opiates play a critical role in the process leading to hyperinsulinemia in hyperandrogenemia.
Sallmén M et al., 2006·Epidemiology (Cambridge, Mass.)
Overweight and obese men have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility. We examined the relationship between male body mass index (BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife <40 years old) with an attempt at pregnancy in the last 4 years based on pregnancy and fertility data provided by wives. Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression. Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01-1.25; n = 1329). There was a dose-response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association. This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment.
To evaluate whether the use of 17alpha-hydroxyprogesterone caproate for the prevention of recurrent preterm deliveries is cost-effective. Using decision-analysis modeling, we compared the cost-effectiveness of using 17alpha-hydroxyprogesterone 1) Prior preterm deliveries less than 32 weeks; 2) prior preterm deliveries 32-37 weeks; 3) prior term delivery; and 4) no prior delivery. Each subgroup was compared with a "no treatment" group. Costs included those for 17alpha-hydroxyprogesterone caproate, hospital admissions, and complications from preterm deliveries. The main outcome measures include cost per quality-adjusted life-year gained and the number of preterm deliveries prevented. Secondary outcomes include neonatal complications prevented. One-way and multiway sensitivity analyses were performed. The use of 17alpha-hydroxyprogesterone caproate for the prevention of preterm deliveries result in cost-savings in women with prior preterm deliveries less than 32 weeks and 32-37 weeks. The sensitivity analyses revealed the model to be robust over a wide range of values for evaluated variables. Within our baseline assumptions, 17alpha-hydroxyprogesterone caproate was associated with cost-savings when used for the prevention of preterm deliveries in women with prior preterm deliveries.
Contraception/ComparisonGeneral OB/GYNReproductive Endocrinology
Open Access
It has been suggested that hormonal risk factors act predominantly on estrogen receptor and progesterone receptor (ER/PR)-positive breast cancers. However, the data have been inconsistent, especially in younger women. We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients. We used multivariable unconditional logistic regression methods to conduct case-control comparisons overall as well as by
Thyroid disease in general, and hypothyroidism in particular, are very common in women. In the USA, the most common cause of primary thyroid deficiency is on an autoimmune basis due to lymphocytic (Hashimoto) thyroiditis. Because there are thyroid hormone receptors in virtually every tissue of the body, the manifestations of hypothyroidism are varied, but problems with abnormal menses, conception, fertility, and pregnancy can be especially troubling in young women. The single most important diagnostic test is measurement of serum thyrotropin (TSH). The overwhelming majority of patients with hypothyroidism are treated with a single daily dose of synthetic levothyroxine with the goal of therapy being restoration of a normal metabolic state with return of the TSH level down to the range of 0.5 to 1.5 mlU/L. "Subclinical" hypothyroidism refers to those patients with early or mild thyroid hypofunction manifested as slight elevations of thyrotropin (approximately 4-10 mlU/L) although serum thyroxine (T4) and triiodothyronine (T3) levels are within their reference ranges. The entity is somewhat controversial in regard to its consequences if left untreated, and whether or not we should be screening patients, at least susceptible populations, for the condition. Reports indicate an association between subclinical hypothyroidism and poor outcomes of pregnancy, as well as dyslipidemias, atherogenesis, and increased mortality in the long term. We believe these consequences are sufficiently compelling to warrant screening and treatment with levothyroxine when found to halt progression to overt hypothyroidism, and improve symptoms, pregnancy outcomes, lipid abnormalities, and cardiovascular function. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to recall that hypothyroidism is a common disease in women, has many protean manifestations, and can be successfully diagnosed and treated; explain that the condition of subclinical hypothyroidism can be diagnosed and if treated can prevent many untoward complications; and state that there should be heightened awareness of the disease so that proper screening tests can be performed.