Differential changes in appetite hormones post-prandially based on menstrual cycle phase and oral contraceptive use: A preliminary study.

This was a preliminary study that examined whether appetite regulation is altered during the menstrual cycle or with oral contraceptives. Ten naturally cycling females (NON-USERS) and nine tri-phasic oral contraceptive using females (USERS) completed experimental sessions during each menstrual phase (follicular phase: FP; ovulatory phase: OP; luteal phase: LP). Appetite perceptions and blood samples were obtained fasted, 30, 60, and 90 min post-prandial to measure acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and total peptide tyrosine tyrosine (PYY). Changes were considered important if p < 0.100 and the effect size was ≥medium. There appeared to be a three-way (group x phase x time) interaction for acylated ghrelin where concentrations appeared to be greater in USERS versus NON-USERS during the OP 90-min post-prandial and during the LP fasted, and 90-min post-prandial. In USERS, ghrelin appeared to be greater 90-min post-prandial in the OP versus the FP with no other apparent differences between phases. There were no apparent differences between phases in NON-USERS. There appeared to be a three-way interaction for PYY where concentrations appeared to be greater in USERS during the FP 60-min post-prandial and during the OP 30-min post-prandial. In USERS PYY appeared to be greater 60-min post-prandial during the OP versus the LP with no other apparent differences. There were no apparent differences between phases in NON-USERS. There appeared to be no effect of group or phase on GLP-1, or appetite perceptions. These data demonstrate small effects of menstrual cycle phase and oral contraceptive use on the acylated ghrelin and total PYY response to a standardized meal, with no effects on active GLP-1 or perceived appetite, though more work with a large sample size is necessary.

Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

PURPOSE: Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. METHODS: Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. RESULTS: In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3-4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48-49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7-10% increase in AUC of EES; and a 19% increase in Cmax and 29-42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. CONCLUSION: Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Testing effects of partner support and use of oral contraception during relationship formation on severity of nausea and vomiting in pregnancy.

BACKGROUND: A recent study focusing on dietary predictors of nausea and vomiting in pregnancy (NVP) found that women with higher levels of partner support, and those who had used oral contraception (OC) when they met the father, both tended to report less severe NVP compared with previous non-users or those with less supportive partners. We provide a further test of these factors, using a large sample of women from four countries who retrospectively scored their NVP experience during their first pregnancy. METHODS: We recruited women who had at least one child to participate in a retrospective online survey. In total 2321 women completed our questionnaire including items on demographics, hormonal contraception, NVP, and partner support. We used general linear models and path analysis to analyse our data. RESULTS: Women who had used OC when they met the father of their first child tended to report lower levels of NVP, but the effect size was small and did not survive adding the participant's country to the model. There was no relationship between NVP and partner support in couples who were still together, but there was a significant effect among those couples that had since separated: women whose ex-partner had been relatively supportive reported less severe NVP. Additional analyses showed that women who were older during their first pregnancy reported less severe NVP, and there were also robust differences between countries. CONCLUSIONS: These results provide further evidence for multiple influences on women's experience of NVP symptoms, including levels of perceived partner support.

Oral contraceptive use during relationship formation and current relationship satisfaction: Testing the congruency hypothesis in couples attending pregnancy and fertility clinics.

According to the congruency hypothesis, relationship satisfaction is predicted by the congruency (or non-congruency) between current use of oral contraceptives (OC) and their use during relationship formation. This is based on findings that OC may alter women's mate preferences, so that attraction to their partner may have changed in non-congruent women. Indeed, some studies find that women in a non-congruent state were less sexually satisfied with their partner, although they were more satisfied in non-sexual aspects of the relationship. However, some other studies have produced null results, calling the hypothesis into question. In this study, we tested the congruency hypothesis in two samples of pregnant women, and in two samples of couples attending a fertility clinic. In all four samples, couples completed questionnaires on relationship and sexual satisfaction and the women also reported their previous and current contraceptive use. In one sample of pregnant women, we found that women who used OC during relationship formation were more sexually satisfied with their partner compared to women who did not use OC at that time; this pattern has previously been interpreted as supporting the congruency hypothesis in view of certain similarities in hormonal profile between OC use and pregnancy. We did not find any significant effect of OC use during relationship formation on sexual and relationship satisfaction in the other sample of pregnant women, either sample attending the fertility clinic, or in the male partners of any of our samples. Our results thus provide mixed support for the congruency hypothesis. Finally, we discuss recommendations for future studies such as use of within-subject designs and more structured assessment of sexual satisfaction.

Associations of Oral Contraceptives with Mammographic Breast Density in Premenopausal Women.

BACKGROUND: We investigated the associations of oral contraceptives (OC) with percent breast density (PD), absolute dense area (DA), nondense area (NDA), and a novel image intensity variation (V) measure in premenopausal women. METHODS: This study included 1,233 controls from a nested case-control study within Nurses' Health Study II cohort. Information on OCs was collected in 1989 and updated biennially. OC use was defined from the questionnaire closest to the mammogram date. PD, DA, and NDA were measured from digitized film mammograms using a computer-assisted thresholding technique; the V measure was obtained with a previously developed algorithm measuring the SD of pixel values in the eroded breast region. Generalized linear regression was used to assess associations between OCs and density measures (square root-transformed PD, DA, and NDA, and -untransformed V). RESULTS: OC use was not associated with PD [current vs. never: ß = -0.06; 95% confidence interval (CI), -0.37-0.24; past vs. never: ß = 0.10; 95% CI, -0.09-0.29], DA (current vs. never: ß = -0.20; 95% CI -0.59-0.18; past vs. never: ß = 0.13; 95% CI, -0.12-0.39), and NDA (current vs. never: ß = -0.19; 95% CI, -0.56-0.18; past vs. never: ß = -0.01; 95% CI, -0.28-0.25). Women with younger age at initiation had significantly greater V-measure (<20 years vs. never: ß = 26.88; 95% CI, 3.18-50.58; 20-24 years vs. never: ß = 20.23; 95% CI, -4.24-44.71; 25-29 years vs. never: ß = 2.61; 95% CI -29.00-34.23; ≥30 years vs. never: ß = 0.28; 95% CI, -34.16-34.72, P trend = 0.03). CONCLUSIONS: Our findings suggest that an earlier age at first OC use was associated with significantly greater V. IMPACT: These findings could guide decisions about the age for OC initiation.

Manejo farmacológico del sangrado irregular no menstrual asociado al uso de implantes anticonceptivos subdérmicos / Pharmacological management of irregular non-menstrual bleeding associated with the use of subdermal contraceptive implants

El spottingo sangrado irregular no menstrual es uno de los principales efectos secundarios de los implantes anticonceptivos, situación que se recomienda discutir con la usuaria previo a la colocación, para evitar falsas expectativas o temores que lleven a la extracción temprana del dispositivo. A propósito de una paciente sin antecedentes relevantes que consultó al centro de salud por spotting desde la colocación del implante cuatro meses antes, decidimos revisar la evidencia sobre la efectividad de los distintos esquemas farmacológicos disponibles para el manejo de este evento adverso. Luego de realizar una búsqueda bibliográfica concluimos que, si bien existe sustento para indicar algunos de los esquemas farmacológicos, este es aún débil y son necesarios estudios clínicos adicionales que brinden evidencia sólida sobre qué esquema en particular utilizar, evaluando sus riesgos y beneficios. (AU)

Spotting or irregular non-menstrual bleeding is one of the main side effects of contraceptive implants, a situation that health professionals must discuss with the user prior to its placement in order to avoid false expectations or fears that lead to early removal of the implant. Regarding a patient with no relevant history who consulted the health center due to spotting four months after implant placement, we decided to review the evidence onthe effectiveness on different pharmacological schemes available for the management of this adverse event. After performing a literature search, we concluded that, although there is support for indicating some of the pharmacological schemes, this is still weak, and further clinical studies are needed to provide solid evidence on which particular scheme touse, assessing its risks and benefits. (AU)

Treatment of lean PCOS teenagers: a follow-up comparison between Myo-Inositol and oral contraceptives.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder widely diffused and diagnosed in women of reproductive age. The pathology exhibits alteration of the reproductive functions, including conditions as hyperandrogenism, menstrual cycle irregularity, type 2 diabetes. These conditions are visible in the patients through phenotypical manifestations as hirsutism, acne, and obesity. Even if the syndrome is characterized by common features among both adult and adolescent women, the diagnostic criteria are different for the two age categories and to date still controversial. We investigated different treatments in PCOS adolescents with non-severe metabolic conditions, to evaluate which could be the appropriate therapeutical approach for these patients. PATIENTS AND METHODS: We enrolled lean teenagers with PCOS, and we divided the patients in two age ranges: 13-16 years old and 17-19 years old. They were treated for 3 months either with oral contraceptive pills (OCP) drospirenone/ethinylestradiol (group A), myo-Inositol (myo-Ins) (group B), or OCP plus myo-Ins (group C). Data were analyzed with a descriptive statistics summarizing quantitative variables including median, 25th and 75th percentiles. RESULTS: We pointed out that the group of 13-16 years old lean teenagers treated with myo-Ins exhibit a significant decrease of weight and body mass index (BMI), and an effective improvement the metabolic and hormonal parameters achieved with a non-pharmacological treatment. In the older teenagers aged 17-19 years, data highlights that myo-Ins treatment in combination with OCP prevents the increases of weight and BMI, improves the metabolic profile of the patients, and strongly ameliorates the hormonal parameters analyzed. CONCLUSIONS: The results indicate a different scenario in the two age ranges considered and interestingly suggest an important role of myo-Ins in the PCOS context. A therapy based on this natural compound alone or in combination with OCP seems effective to improve both metabolic and hormonal parameters of PCOS adolescents and thus could represent a novel and valid option to consider for the treatment of this syndrome.

Oral Contraceptive Intake and Iodine Status in Young Women.

OBJECTIVE: Similar to pregnant women, women taking an oral contraceptive (OC) might have elevated iodine requirements due to the altered hormonal state. This is the first study aimed at investigating the prevalence of iodine deficiency and possible influences of OC intake on urine creatinine and iodine levels in young women. METHODS: One hundred fifty-five women between the age of 18 and 35 years (62 taking an OC and 93 controls) participated in a cross-sectional pilot study at the Medical University of Vienna, which included a 1-spot urine sample and a questionnaire on OC intake as well as a food questionnaire. RESULTS: The median urinary iodine concentration (UIC) in this study was 68 µg/L (41, 111 µg/L) suggesting an inadequate iodine status in the women according to the WHO guidelines. Median UIC (OC: 89 µg/L, IQR 55-120; control: 59 µg/L, IQR 39-91, p = 0.010) and urine creatinine (OC: median = 99.0 µg/L, IQR 74.9-175.5; control: 77.0 µg/L, IQR 49.6-147.2, p = 0.030) levels were significantly higher in OC women than in the control group. UIC corrected for urine creatinine was comparable between both groups. CONCLUSION: With similar creatinine-corrected UICs in both groups, OC intake might not have a significant impact on iodine status. However, the low median UIC in a vulnerable group of young women potentially conceiving in the following years points at the necessity of optimizing the iodine intake in the Austrian population and reiterates the insufficiency of the current iodine supplementation measures.

Oral contraceptives, depressive and insomnia symptoms in adult women with and without depression.

BACKGROUND: Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for major depressive disorder (MDD) but may also be a symptom of the disorder. Despite the large number of women who use OC, it is yet unknown whether women with previous or current diagnosis of depression are more likely to experience more severe depressive and insomnia symptoms during concurrent OC use than women without diagnosis of depression. AIM: This study examined associations between OC use and concurrent symptoms of depression (including atypical depression) and insomnia as well as between OC and prevalences of concurrent dysthymia and MDD. Participants were adult women with and without a history of MDD or dysthymia. We hypothesized that OC use is associated with concurrent increased severity of depressive symptoms and insomnia symptoms, as well as with an increased prevalence of concurrent diagnoses of dysthymia and MDD. We also hypothesized that a history of MDD or dysthymia moderates the relationship between OC use and depressive and insomnia symptoms. METHODS: Measurements from premenopausal adult women from the Netherlands Study of Depression and Anxiety (NESDA) were grouped, based on whether participants were using OC or naturally cycling (NC). OC use, timing and regularity of the menstrual cycle were assessed with a structured interview, self-reported symptoms of depression (including atypical depression), insomnia with validated questionnaires, and MDD and dysthymia with structured diagnostic interviews. RESULTS: We included a total of 1301 measurements in women who reported OC use and 1913 measurements in NC women (mean age 35.6, 49.8% and 28.9% of measurements in women with a previous depression or current depression, respectively). Linear mixed models showed that overall, OC use was neither associated with more severe depressive symptoms (including atypical depressive symptoms), nor with higher prevalence of diagnoses of MDD or dysthymia. However, by disentangling the amalgamated overall effect, within-person estimates indicated increased depressive symptoms and depressive disorder prevalence during OC use, whereas between-person estimated indicated lower depressive symptoms and prevalence of depressive disorders. OC use was consistently associated with more severe concurrent insomnia symptoms, in the overall estimates as well as in the within-person and between-person estimates. Presence of current or previous MDD or dysthymia did not moderate the associations between OC use and depressive or insomnia symptoms. DISCUSSION: The study findings showed consistent associations between OC use and more severe insomnia symptoms, but no consistent associations between OC and depressive symptoms or diagnoses. Instead, post-hoc analyses showed that associations between OC and depression differed between within- and between person-estimates. This indicates that, although OC shows no associations on the overall level, some individuals might experience OC-associated mood symptoms. Our findings underscore the importance of accounting for individual differences in experiences during OC use. Furthermore, it raises new questions about mechanisms underlying associations between OC, depression and insomnia.

A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors.

PURPOSE: This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives. METHODS: Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis. RESULTS: Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug-drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (Cmax) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration-time curve from time zero to last quantifiable measurement (AUC0-last) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment. CONCLUSION: Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib. ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.

Iron-Containing Oral Contraceptives and Their Effect on Hemoglobin and Biomarkers of Iron Status: A Narrative Review.

Oral contraceptive use has been associated with decreased menstrual blood losses; thus, can independently reduce the risk of anemia and iron deficiency in women. Manufacturers have recently started to include supplemental iron in the non-hormonal placebo tablets of some contraceptives. The aims of this narrative review are: (i) to describe the relationship between oral contraceptive use and both anemia and iron status in women; (ii) to describe the current formulations of iron-containing oral contraceptives (ICOC) available on the market; and (iii) to systematically review the existing literature on the effect of ICOC on biomarkers of anemia and iron status in women. We discovered 21 brands of ICOC, most commonly including 25 mg elemental iron as ferrous fumarate, for seven days, per monthly tablet package. Our search identified one randomized trial evaluating the effectiveness of ICOC use compared to two non-ICOC on increasing hemoglobin (Hb) and iron status biomarker concentrations in women; whereafter 12 months of contraception use, there were no significant differences in Hb concentration nor markers of iron status between the groups. ICOC has the potential to be a cost-effective solution to address both family planning needs and iron deficiency anemia. Yet, more rigorous trials evaluating the effectiveness of ICOC on improving markers of anemia and iron deficiency, as well as investigating the safety of its consumption among iron-replete populations, are warranted.

The use of oral contraceptive is inversely associated with the risk of type 2 diabetes mellitus among middle-aged women.

OBJECTIVE: To assess the cross-sectional association between oral contraceptive (OC) use and type 2 diabetes mellitus (T2DM) risk among US women. METHODS: The data was obtained from the National Health and Nutrition Examination Survey (NHANES 2007-2018). OC use was assessed by questionnaires and the diagnosis of T2DM was confirmed by the glycosylated hemoglobin, fasting blood glucose, and self-report. Binary logistic regression models and the restricted cubic spline model were adopted to evaluate whether OC use was associated with T2DM. RESULTS: Compared with non-users, the odds ratio (OR) with 95% confidence interval (CI) of T2DM risk for the OC users was 0.71 (0.57-0.89) in unadjusted Model. The association remained significant in fully adjusted models, and the OR with 95%CI was 0.78 (0.62-0.99). In the stratified analyses, there was an inverse association of OC use with T2DM risk when women were overweight. Dose-response analysis also revealed an inversely nonlinear relationship between the duration of OC use and T2DM (p-value for linearity = .589). CONCLUSIONS: Our findings suggested that OC use may be inversely associated with T2DM risk.

Do oral contraceptives affect young women's memory? Dopamine-dependent working memory is influenced by COMT genotype, but not time of pill ingestion.

BACKGROUND: Despite the widespread use of oral contraceptives (OCs), and the well-documented influence of estrogens, notably 17ß-estradiol (E2), on cognition, research relating OCs to working memory is limited and mixed. Two factors may contribute to these mixed findings: 1) pharmacokinetics of oral contraceptives, which drive fluctuations in synthetic hormone levels; and 2) genetic polymorphisms related to dopamine degradation and working memory, which interact with E2. This research investigated whether the pharmacokinetics of oral contraceptives, in concert with the single nucleotide polymorphism (Val158Met; rs4680) of the catechol-o-methyltransferase gene (COMT), influence working memory performance. METHODS: University-age women taking and not taking OCs were tested for working memory and genotyped for COMT. If they were not taking OCs (n = 62), sessions occurred in the early follicular (low E2) and late follicular (high E2) phase. If they were taking OCs (n = 52), sessions occurred 1-2 hours after (high ethinyl estradiol, EE) and ~24 hours after (low EE) pill ingestion. Working memory was tested using the N-back, AX-CPT, Digit Span, and Digit Ordering Tasks. Data were analyzed using multilevel models with estrogen condition, COMT, and group as predictors, controlling for mood and practice effects. RESULTS: For women taking OCs, time of pill ingestion did not influence performance. However, the subgroup with COMT val/val (low dopamine) were less accurate on 2-back lure trials than those with COMT met/met (high dopamine). For women not taking OCs, cycle phase moderated COMT's influence on lure accuracy. When compared, women taking OCs had higher AX-CPT proactive control indices than those not taking OCs. CONCLUSION: These findings suggest that oral contraceptives are not detrimental for young women's working memory and that they may increase proactive control. The more pronounced effects of COMT in women taking OCs suggests that, in women taking OCs, suppressed endogenous E2-not fluctuating EE levels-may be more relevant for working memory. Future studies are needed to differentiate effects of endogenous versus synthetic estrogens on working memory.

Adaptation and validation of simple tools to screen and monitor for oral PrEP adherence.

INTRODUCTION: Oral, vaginal and other pre-exposure prophylaxis (PrEP) products for HIV prevention are in various stages of development. Low adherence poses a serious challenge to successful evaluation in trials. In a previous study, we developed tools to screen for general adherence and specifically monitor intravaginal ring adherence within the context of HIV prevention clinical trials. This study aimed to further validate the screening tool and to adapt and provide initial psychometric validation for an oral pill monitoring tool. MATERIALS AND METHODS: We administered a cross-sectional survey between June and October 2018 at a trial site located near Cape Town, South Africa, and another in Thika, Kenya, with 193 women who had experience using daily oral pills. We fit confirmatory factor analysis models on the screening tool items to assess our previously-hypothesized subscale structure. We conducted an exploratory factor analysis of oral PrEP monitoring items to determine the underlying subscale structure. We then assessed the construct validity of each tool by comparing subscales against each other within the current sample and against our original sample, from a study conducted in four sites in South Africa, including Cape Town. RESULTS: The screening tool structure showed moderate evidence of construct validity. As a whole, the tool performed in a similar way to the original sample. The monitoring tool items, which were revised to assess perceptions about and experiences using daily oral PrEP, factored into five subscales that showed moderate to good reliability. Four of the five subscales had a similar structure overall to the vaginal ring monitoring tool from which they were adapted. CONCLUSIONS: Accurate measurement of HIV-prevention product adherence is of critical importance to the assessment of product efficacy and safety in clinical trials, and the support of safe and effective product use in non-trial settings. In this study, we provide further validation for these measures, demonstrating the screening tool's utility in additional populations and adapting the monitoring tool's utility for different HIV-prevention products.

The difficult journey to treatment for women suffering from heavy menstrual bleeding: a multi-national survey.

PURPOSE: Up to 30% of women of reproductive age experience HMB, which has a substantial impact on their quality of life. A clinical care pathway for women with HMB is an unmet need, but its development requires better understanding of the factors that characterise current diagnosis and management of the condition. MATERIALS AND METHODS: This observational, survey-based study assessed the burden, personal experiences, and path through clinical management of women with HMB in Canada, the USA, Brazil, France and Russia using a detailed, semi-structured online questionnaire. After excluding those reporting relevant organic pathology, responses to the questionnaire from 200 women per country were analysed. RESULTS: Around 75% of women with HMB had actively sought information about heavy periods, mostly through internet research. The mean time from first symptoms until seeking help was 2.9 (Standard deviation, 3.1) years. However, 40% of women had not seen a health care professional about the condition. Furthermore, 54% had never been diagnosed or treated. Only 20% had been diagnosed and received appropriate treatment. Treatment was successful in 69% of those patients currently receiving treatment. Oral contraceptives were the treatment most commonly prescribed for HMB, although the highly effective levonorgestrel-intrauterine system was used by only a small proportion of women. CONCLUSIONS: This study provides insight into the typical journey of a woman with HMB which may help patients and health care professionals improve the path to diagnosis and treatment, although further research with long-term outcomes is needed.

Effects of oral contraceptive for different responder women before GnRH antagonists: a systematic review and meta-analysis.

This analysis aimed to compare the efficacy of oral contraceptive pill (OCP) pretreatment for gonadotropin-releasing hormone antagonist (GnRH-ant) protocol, especially for different responder women. The PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for trials on with and without OCP pretreatment before stimulation with gonadotropins. The standardized mean differences (SMDs) or pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used for statistical analysis. Fifteen studies with 5326 in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were summarized. The clinical pregnancy rate, moderate or severe ovarian hyper-stimulation syndrome (OHSS) rate, and miscarriage rate was not found to be significantly different between patients with and those without OCP pretreatment, even after sensitivity analyses. In addition, there were still no statistically significant differences for the subgroups analyses of hyper-responders, poor responders, and normal responders. No significant differences were detected in the duration of ovarian stimulation, gonadotropin dose consumed, endometrial thickness on day of oocyte collection, or number of oocytes. This meta-analysis did not find an unequivocally beneficial effect of OCP pretreatment for different responder women with using a GnRH-ant protocol. The clinician should weigh the advantages and disadvantages of OCP pretreatment and guide the treatment scheduling considering the patient's own situation.

Cardiorespiratory response to exercise in endurance-trained premenopausal and postmenopausal females.

PURPOSE: To assess the influence of different hormonal profiles on the cardiorespiratory response to exercise in endurance-trained females. METHODS: Forty-seven eumenorrheic females, 38 low-dose monophasic oral contraceptive (OC) users and 13 postmenopausal women, all of them endurance-trained, participated in this study. A DXA scan, blood sample tests and a maximal aerobic test were performed under similar low-sex hormone levels: early follicular phase for the eumenorrheic females; withdrawal phase for the OC group and at any time for postmenopausal women. Cardiorespiratory variables were measured at resting and throughout the maximal aerobic test (ventilatory threshold 1, 2 and peak values). Heart rate (HR) was continuously monitored with a 12-lead ECG. Blood pressure (BP) was measured with an auscultatory method and a calibrated mercury sphygmomanometer. Expired gases were measured breath-by-breath with the gas analyser Jaeger Oxycon Pro. RESULTS: One-way ANCOVA reported a lower peak HR in postmenopausal women (172.4 ± 11.7 bpm) than in eumenorrheic females (180.9 ± 10.6 bpm) (p = 0.024). In addition, postmenopausal women exhibited lower VO2 (39.1 ± 4.9 ml/kg/min) compared to eumenorrheic females (45.1 ± 4.4 ml/kg/min) in ventilatory threshold 2 (p = 0.009). Nonetheless, respiratory variables did not show differences between groups at peak values. Finally, no differences between OC users and eumenorrheic females' cardiorespiratory response were observed in endurance-trained females. CONCLUSIONS: Cardiorespiratory system is impaired in postmenopausal women due to physiological changes caused by age and sex hormones' decrement. Although these alterations appear not to be fully compensated by exercise, endurance training could effectively mitigate them. In addition, monophasic OC pills appear not to impact cardiorespiratory response to an incremental running test in endurance-trained females.

Contraceptive use and fertility behaviour among Syrian migrant women.

OBJECTIVES: This study aimed to investigate fertility behaviours and contraceptive use among Syrian migrant women in western Turkey. METHODS: An epidemiological, single-centre, cross-sectional, descriptive study was conducted. The survey collected data on sociodemographic characteristics and types of marriage, use of contraceptive methods and fertility behaviours among 223 Syrian migrant women. RESULTS: The women's mean (± standard deviation) age range was 29.6 ± 9.1 (range 18-49) years; 29.6% had no formal marriage status; 61.0% had had an arranged marriage. The mean age at first pregnancy was 19.5 ± 3.4 (13-39) years; 26.4% had become pregnant before the age of 18. In total, 94.2% of participants had knowledge of contraceptive methods. However, 47.5% did not use contraception and the main reason for this was to become pregnant again. Intrauterine devices and oral contraceptive pills were known as contraceptive methods by 67.7% and 72.2% of women, but used by only 16.1% and 8.5%, respectively. Withdrawal (22.0%) was the most used contraceptive method. There was a risk of unwanted pregnancy in 13.0% of participants. Arranged marriage and low educational level were determined to be risk factors for adolescent pregnancy. CONCLUSION: Although Syrian migrant women were aware of contraceptive methods, the rate of method use was low.

Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study.

BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.