The hormonal profile in women using combined monophasic oral contraceptive pills varies across the pill cycle: a temporal analysis of serum endogenous and exogenous hormones using liquid chromatography with tandem mass spectroscopy.

Oral contraceptive pills, of all types, are used by approximately 151 million women worldwide; however, a clear understanding of the concentrations of endogenous and exogenous hormones across a 28-day combination monophasic oral contraceptive pill pack is not well described. In our study of 14 female participants taking various combination monophasic oral contraceptive pills, we found significant fluctuations in endogenous and exogenous hormone levels throughout the pill cycle. Our analysis revealed significantly greater levels of ethinyl estradiol on the 20th and 21st days of active pill ingestion, compared with days 1-2 (active) and days 27-28 (inactive pill ingestion). Conversely, estradiol concentrations decreased during active pill consumption, while progestin and progesterone levels remained stable. During the 7 days of inactive pill ingestion, estradiol levels rose sharply and were significantly higher at days 27-28 compared with the mid and late active phase time points, while ethinyl estradiol declined and progestin did not change. These findings challenge the previous assumption that endogenous and exogenous hormones are stable throughout the 28-day pill cycle.NEW & NOTEWORTHY The results from this study have wide-ranging implications for research and treatment in women's health including considerations in research design and interpretation for studies including women taking oral contraceptives, the potential for more precise and personalized methods of dosing to reduce unwanted side effects and adverse events, and the potential treatment of a variety of disorders ranging from musculoskeletal to neurological with exogenous hormones.

Associations between common contraceptive use and circulating inflammatory biomarkers.

Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor α receptor 2 (sTNFR2), in the Nurses' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors, and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average 30.4% (-53.6, 4.4) with every 5 years since initial IUD use (P-trend=0.03), while CRP increased an average 9.9% (95% CI: 5.7, 14.3) with every 5 years of use of OC (P-trend<0.0001) as well as differences by BMI and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time.

Oral contraceptives in adolescents: a retrospective population-based study on blood pressure and metabolic dysregulation.

PURPOSE: This study aimed to explore the relationship between oral contraceptive use and blood pressure values and in a national cohort of women adolescents and to investigate the level of coexistence of the high blood pressure levels, dyslipidemia or insulin resistance. METHODS: This is a retrospective cohort study that evaluated data form 14,299 adolescents aged 14 to 17 years. Crude and race-and age-adjusted analyses were performed using Poisson regression to estimate the prevalence ratios. Data clustering analysis was performed using machine learning approaches supported by an unsupervised neural network of self-organizing maps. RESULTS: We found that 14.5% (n = 2076) of the women adolescents use oral contraceptives. Moreover, an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance (all P < 0.001) was observed among adolescents who use oral contraceptives as compared to those who do not. Our analysis also showed that 2.3% of adolescents using oral contraceptives had both high blood pressure levels and dyslipidemia, whereas 3.2% had high blood pressure levels combined with insulin resistance (all P < 0.001). The algorithmic investigative approach demonstrated that total cholesterol, LDLc, HDLc, insulin, and HOMA-IR were the most predicted variables to assist classificatory association in the context of oral contraceptive use among women adolescents with high blood pressure. CONCLUSIONS: These findings suggest that oral contraceptives were associated with an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance among women adolescents. Although the indication of this therapy is adequate to avoid unintended pregnancies, their use must be based on rigorous individual evaluation and under constant control of the cardiometabolic risk factors.

Prevalence of anxiety and depression among Lebanese women using oral contraceptives: a cross-sectional study.

BACKGROUND: Oral contraceptives (OCs) are used worldwide, including Lebanese women. However, the association between OCs use and anxiety or depression remains unclear. This study aims to assess the prevalence of anxiety and depression among Lebanese women using oral contraceptive pills and investigate the differential impact of combined oral contraceptives (COCs) versus progestogen-only pills (POPs) on mental health outcomes. METHODS: A cross-sectional study was conducted among a sample of Lebanese women using OCs between January and March 2023. Nine hundred nighty seven out of the 2051 women who took part in the survey met our criteria and were included in this study. Data on anxiety and depression were collected using validated and reliable scales, the Arabic versions of the Generalized Anxiety Disorder-7 Questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Statistical analyses, including multivariate analysis, were performed to assess the association between OCs type (COC vs. POP) and anxiety/depression. RESULTS: The prevalence of anxiety and depression among Lebanese women taking OCs was found to be 39.9% and 64.3%, respectively. Furthermore, the study revealed that POP users had 2.8 times higher odds of developing anxiety (adjusted odds ratio ORadj = 2.8 with 95% confidence interval CI of 1.770 to 4.435) p-value < 0.001 and 9.2 times higher odds of developing depression (adjusted odds ratio ORadj = 9.2 with 95% confidence interval CI of 5.790 to 14.506) p-value < 0.001 compared to COC users. CONCLUSION: The results of this study shed light on the elevated prevalence of anxiety and depression among Lebanese women using OCs and emphasized the varying effects of COCs and POPs on their mental health outcomes. Further research is needed to comprehensively understand this association, considering both the dosage and specific type of oral contraceptive to improve the overall well-being of women using these contraceptives.

Evaluating Patient-Reported Adherence And Safety for Oral Contraception Treatment in Women via a Direct-To-Consumer Prescription Platform: A Cross-Sectional Study.

Background: The acceptance of telemedicine in the German health care system is growing. This also extends to gynecological applications such as the prescription of contraceptives. This study investigates the contraceptive use and adherence of patients using a direct-to-consumer (DTC) prescription platform for oral contraception. Methods: A retrospective cross-sectional study was conducted using anonymized data obtained from a DTC prescription platform between May 2021 and March 2023. The patient-reported outcome was evaluated after 3 months through a follow-up questionnaire. Results: In total, 8,065 patient records were available and 1,008 patients responded to the follow-up questionnaire. Patients were mostly taking combined oral contraceptives (COCs) and only 6% were taking a progestin-only pill (POP). Even in patient populations at higher risk, such as smokers and obese women, the proportion of POP users was less than 20%. Over 90% of users reported that they took the pill without any intake errors, with the main intake error being forgotten intake. Overall, 23% of patients reported adverse events while taking the pill, with POP users reporting more adverse events than COC users (36.7% vs. 22.2%). Over 70% of patients regularly attended cervical screening. Conclusions: Users of a DTC prescribing platform exhibit strong adherence, with over 90% successfully taking oral contraceptive pills. The platform effectively identifies absolute contraindications but could enhance recommendations for contraceptives in the presence of relative contraindications. For healthy women familiar with pill usage, DTC platforms offer a viable and convenient alternative to traditional doctor's office prescriptions.

Health benefits of combined oral contraceptives - a narrative review.

PURPOSE: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. METHODS: We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. RESULTS: We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. CONCLUSIONS: The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription.

Combined oral contraceptives: update recommendations of the Latin American contraceptive association.

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users.Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety.Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'.Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman.Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.

Attitudes of women and pharmacists on the opportunity to obtain a progestogen-only pill over the counter - Italian outcomes.

PURPOSE: Scrutinizing, among potential providers and users, the perceived claim and interest for over the counter (OTC) accessibility of a progestogen-only pill (POP). METHODS: Cross-sectional, descriptive study based on an online survey of 1000 women and 100 pharmacists in Italy, part of a larger sample including Germany and Spain. RESULTS: Hormonal contraceptive methods are used by 35%; 5% of women reported currently not using contraception, 40% using a barrier method, and 20% a method considered less effective than male condoms (including 16% withdrawal and 4% natural methods and fertility/contraceptive applications). Almost 80% of women felt knowledgeable about the different contraceptive method, but about 1/3 had experienced difficulty accessing their oral contraceptive (OC) in the past two years. Women reacted positively to the proposition of an OTC-POP and 85% agreed that they would discuss the decision to buy it with their doctor; 75% reported they would continue to see their doctor for other reproductive health issues, including screening. The most frequent barrier is cost (reported by 25-33% of women) followed by long waiting times for doctor appointments and lack of personal time to schedule an appointment.Pharmacists (66%) would be likely/fairly likely to recommend the POP after appropriate training, agreeing that the benefits of an OTC-POP included improved access for women, saving them time and giving them more independence. CONCLUSIONS: Potential users of contraception in Italy have a positive attitude toward OTC-POP, with doctors continuing to have a relevant role. Following training, pharmacists are also positive.

Oral contraceptive use and risk of suicidal behavior among young women.

BACKGROUND: Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. METHODS: We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. RESULTS: In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. CONCLUSIONS: Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.

Oral contraceptive use by formulation and breast cancer risk by subtype in the Nurses' Health Study II: a prospective cohort study.

BACKGROUND: Oral contraceptive use has been associated with a higher breast cancer risk; however, evidence for the associations between different oral contraceptive formulations and breast cancer risk, especially by disease subtype, is limited. OBJECTIVE: This study aimed to evaluate the associations between oral contraceptive use by formulation and breast cancer risk by disease subtype. STUDY DESIGN: This prospective cohort study included 113,187 women from the Nurses' Health Study II with recalled information on oral contraceptive usage from 13 years of age to baseline (1989) and updated data on usage until 2009 collected via biennial questionnaires. A total of 5799 breast cancer cases were identified until the end of 2017. Multivariable Cox proportional hazards models estimated hazard ratios and 95% confidence intervals for the associations between oral contraceptive use and breast cancer risk overall and by estrogen and progesterone receptor and human epidermal growth factor receptor 2 status. Oral contraceptive use was evaluated by status of use (current, former, and never), duration of and time since last use independently and cross-classified, and formulation (ie, estrogen and progestin type). RESULTS: Current oral contraceptive use was associated with a higher risk for invasive breast cancer (hazard ratio, 1.31; 95% confidence interval, 1.09-1.58) when compared with never use, with stronger associations observed for longer durations of current use (>5 years: hazard ratio, 1.56; 95% confidence interval, 1.23-1.99; ≤5 years: hazard ratio, 1.19; 95% confidence interval, 0.95-1.49). Among former users with >5 years since cessation, the risk was similar to that of never users (eg, >5 to 10 years since cessation: hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). Associations did not differ significantly by tumor subtype. In analyses by formulation, current use of formulations containing levonorgestrel in triphasic (hazard ratio, 2.83; 95% confidence interval, 1.98-4.03) and extended cycle regimens (hazard ratio, 3.49; 95% confidence interval, 1.28-9.53) and norgestrel in monophasic regimens (hazard ratio, 1.91; 95% confidence interval, 1.19-3.06), all combined with ethinyl estradiol, was associated with a higher breast cancer risk when compared with never oral contraceptive use. No association was observed for current use of the other progestin types evaluated (norethindrone, norethindrone acetate, ethynodiol diacetate, desogestrel, norgestimate, and drospirenone), however, sample sizes were relatively small for some of the subgroups, limiting these analyses. CONCLUSION: Current oral contraceptive use was associated with a higher risk for invasive breast cancer regardless of disease subtype, however, the risk in former users was comparable with never users 5 years after cessation. In analyses by progestin type, associations were observed for select formulations containing levonorgestrel and norgestrel. Assessment of the associations for newer progestin types (desogestrel, norgestimate, drospirenone) was limited by sample size, and further research on more recently introduced progestins is warranted.

Who is providing contraception care in the United States? An observational study of the contraception workforce.

BACKGROUND: Contraception care is essential to providing comprehensive healthcare; however, little is known nationally about the contraception workforce. Previous research has examined the supply, distribution, and adequacy of the health workforce providing contraception services, but this research has faced a series of data limitations, relying on surveys or focusing on a subset of practitioners and resulting in an incomplete picture of contraception practitioners in the United States. OBJECTIVE: This study aimed to construct a comprehensive database of the contraceptive workforce in the United States that provides the following 6 types of highly effective contraception: intrauterine device, implant, shot (depot medroxyprogesterone acetate), oral contraception, hormonal patch, and vaginal ring. In addition, we aimed to examine the difference in supply, distribution, the types of contraception services offered, and Medicaid participation. STUDY DESIGN: We constructed a national database of contraceptive service providers using multiple data sets: IQVIA prescription claims, preadjudicated medical claims, and the OneKey healthcare provider data set; the National Plan and Provider Enumeration System data set; and the Census Bureau's American Community Survey data on population demographics. All statistical analyses were descriptive, including chi-squared tests for groupwise differences and pairwise post hoc tests with Bonferroni corrections for multiple comparisons. RESULTS: Although 73.1% of obstetrician-gynecologists and 72.6% of nurse-midwives prescribed the pill, patch, or ring, only 51.4% of family medicine physicians, 32.4% of pediatricians, and 19.8% of internal medicine physicians do so. The ratio of all primary care providers prescribing contraception to the female population of reproductive age (ages, 15-44 years) varied substantially across states, with a range of 27.9 providers per 10,000 population in New Jersey to 74.2 providers per 10,000 population in Maine. In addition, there are substantial differences across states for Medicaid acceptance. Of the obstetrician-gynecologists providing contraception, the percentage of providers who prescribe contraception to Medicaid patients ranged from 83.9% (District of Columbia) to 100% (North Dakota); for family medicine physicians, it ranged from 49.7% (Florida) to 91.1% (Massachusetts); and for internal medicine physicians, it ranged from 25.0% (Texas) to 75.9% (Delaware). For in-person contraception, there were large differences in the proportion of providers offering the 3 different contraceptive method types (intrauterine device, implant, and shot) by provider specialty. CONCLUSION: This study found a significant difference in the distribution, types of contraception, and Medicaid participation of the contraception workforce. In addition to obstetrician-gynecologists and nurse-midwives, family medicine physicians, internal medicine physicians, pediatricians, advanced practice nurses, and physician assistants are important contraception providers. However, large gaps remain in the provision of highly effective services such as intrauterine devices and implants. Future research should examine provider characteristics, programs, and policies associated with the provision of different contraception services.

Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia.

OBJECTIVES: To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. DESIGN: Multicenter, open-label, phase 3 trial. SETTING: Sixty-nine sites in Europe and Russia. POPULATION: Sexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 . METHODS: E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary. MAIN OUTCOME MEASURES: Pearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs. RESULTS: A total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events. CONCLUSION: E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile. TWEETABLE ABSTRACT: A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation: A randomized clinical trial.

INTRODUCTION: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. MATERIAL AND METHODS: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). CLINICAL TRIAL REGISTRATION: NCT02352090. RESULTS: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. CONCLUSIONS: Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.

The views of women and pharmacists on the desirability of a progestogen-only pill over the counter. Results of a survey in Germany, Italy and Spain.

PURPOSE: To explore the perceived need and enthusiasm for over the counter (OTC) progestogen-only pills (POP). MATERIALS AND METHODS: A web-based survey of 1000 sexually active women (16-45) and 100 pharmacists in Germany, Italy and Spain. RESULTS: Despite not wanting to conceive, 5-6% of women in each country were not using contraception and 8-20% were using methods less effective than condoms. At least 74% of respondents felt knowledgeable about the different contraceptives available but at least 1/3 had experienced difficulty accessing oral contraceptive (OCs) in the past two years. The cost of contraceptives, the need to see a doctor and long waits for appointments were cited as barriers for not using OCs. The majority agreed they would discuss with their doctor the decision to buy the POP, consult about side effects and other reproductive health issues. Over 2/3 of pharmacists in each country would be very, or fairly, likely to recommend the POP, agreeing that the benefits included improved access for women, and offered them more independence. CONCLUSIONS: Asked directly, women in Germany, Spain and Italy currently using contraception are positive about a POP OTC. Pharmacists are also positive, with the overwhelming majority in favour of providing POPs.

Hypertension and Reproduction.

PURPOSE OF REVIEW: Many aspects of reproduction have been associated with increased blood pressure and impaired glucose metabolism that reveals a subsequent increased risk of cardiovascular disease. The aim of this review is to assess reproductive life factors associated with an increased risk of hypertension and cardiovascular disease, e.g., early life programming, sexual, and reproductive health in men and women. RECENT FINDINGS: Impaired fetal growth, with low birth weight adjusted for gestational age, has been found associated with hypertension in adulthood. Erectile dysfunction, currently considered an early diagnostic marker of cardiovascular disease preceding the manifestation of coronary artery disease by several years, frequently coexisting with hypertension, could also be exacerbated by some antihypertensive drugs. Male hypogonadism or subfertility are associated with increased cardiovascular risk. Hypertensive disorders in pregnancy including preeclampsia represent a major cause of maternal, fetal and neonatal morbidity, and mortality. The risk of developing preeclampsia can be substantially reduced in women at its high or moderate risk with a low dose of acetylsalicylic acid initiated from 12 weeks of gestation. An increased risk of hypertension in women following invasive-assisted reproductive technologies has been newly observed. Blood pressure elevation has been noticed following contraceptive pill use, around the menopause and in postmenopausal age. Furthermore, drug treatment of hypertension has to be considered as a factor with a potential impact on reproduction (e.g., due to teratogenic drug effects). In summary, a deeper understanding of reproductive life effects on hypertension and metabolic abnormalities may improve prediction of future cardiovascular disease.

Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review.

PURPOSE: BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general population. This review analyses the published data on OC and risk of cancer in BRCA mutation carriers. METHODS: We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library. RESULTS: We included four meta-analyses, one review, one case-control study and one retrospective cohort study on the association between ovarian cancer and OC in BRCA mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case-control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in BRCA mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC. CONCLUSION: Oral contraception leads to a risk reduction of ovarian cancer also in BRCA mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.

On exercise thermoregulation in females: interaction of endogenous and exogenous ovarian hormones.

KEY POINTS: One in two female athletes chronically take a combined, monophasic oral contraceptive pill (OCP). Previous thermoregulatory investigations proposed that an endogenous rhythm of the menstrual cycle still occurs with OCP usage. Forthcoming large international sporting events will expose female athletes to hot environments differing in their thermal profile, yet few data exist on how trained women will respond from both a thermoregulatory and performance stand-point. In the present study, we have demonstrated that a small endogenous rhythm of the menstrual cycle still affects Tcore and also that chronic OCP use attenuates the sweating response, whereas behavioural thermoregulation is maintained. Furthermore, humid heat affects both performance and thermoregulatory responses to a greater extent than OCP usage and the menstrual cycle does. ABSTRACT: We studied thermoregulatory responses of ten well-trained ( V̇O2max , 57 ± 7 mL min-1  kg-1 ) women taking a combined, monophasic oral contraceptive pill (OCP) (≥12 months) during exercise in dry and humid heat, across their active OCP cycle. They completed four trials, each of resting and cycling at fixed intensities (125 and 150 W), aiming to assess autonomic regulation, and then a self-paced intensity (30-min work trial) to assess behavioural regulation. Trials were conducted in quasi-follicular (qF) and quasi-luteal (qL) phases in dry (DRY) and humid (HUM) heat matched for wet bulb globe temperature (WBGT) (27°C). During rest and exercise at 125 W, rectal temperature was 0.15°C higher in qL than qF (P = 0.05) independent of environment (P = 0.17). The onset threshold and thermosensitivity of local sweat rate and forearm blood flow relative to mean body temperature was unaffected by the OCP cycle (both P > 0.30). Exercise performance did not differ between quasi-phases (qF: 268 ± 31 kJ, qL: 263 ± 26 kJ, P = 0.31) but was 5 ± 7% higher during DRY than during HUM (273 ± 29 kJ, 258 ± 28 kJ; P = 0.03). Compared to matched eumenorrhoeic athletes, chronic OCP use impaired the sweating onset threshold and thermosensitivity (both P < 0.01). In well-trained, OCP-using women exercising in the heat: (i) a performance-thermoregulatory trade-off occurred that required behavioural adjustment; (ii) humidity impaired performance as a result of reduced evaporative power despite matched WBGT; and (iii) the sudomotor but not behavioural thermoregulatory responses were impaired compared to matched eumenorrhoeic athletes.

Novel Insights on Sex-Related Differences in Asthma.

PURPOSE OF REVIEW: Asthma, a common respiratory disease that affects about 10% of the US population, represents a significant public health issue. In the last decade, cumulative evidence has demonstrated sex disparities in asthma, including significant differences in epidemiology, clinical presentation, response to therapies, and health outcomes. Understanding sex-related differences in asthma enables clinicians to provide personalized asthma care and improve asthma outcome. RECENT FINDINGS: Recent studies on sex-related differences in asthma inform us on mechanism underlying asthma pathogenesis across all age groups. Sex hormones directly modulate immune pathways crucial in asthma pathogenesis and affect individual's response to environmental triggers and medications, such as leukokotriene inhibitors. Not surprisingly, the use of external sex hormone supplementations appears to modulate asthma risk. Identification of sex-specific asthma risk loci through genome-wide association studies also provides supporting evidence on sex-related differences in asthma. There is an interaction between sex and obesity, an interaction that could place females at higher risk for systemic inflammation and, consequently, asthma. In this article, we review epidemiological and clinical studies on sex-related differences in asthma, with a special focus on the role of sex hormones, including hormonal therapies and the asthma-obesity interaction.

Hormonal oral contraceptive influence on isolation, Characterization and cryopreservation of mesenchymal stem cells from menstrual fluid.

The purpose of the study was to evaluate whether the intake of hormonal oral contraceptive influences the viability of mesenchymal stem cell. Sixteen healthy female volunteers with regular menstrual cycles were invited to participate. Menstrual fluid was collected on the day of maximum flux, and collected cells were analyzed by a 'minimal standard' for MSC characterization: plastic adherence, trilineage (adipogenic, osteogenic, chondrogenic) in vitro differentiation and a minimalistic panel of markers assessed by flow cytometry (CD731, CD901, CD1051, CD34-, CD45-) using monoclonal antibodies. The participants were divided into two groups: Group 1 - no hormonal contraceptive use; Group 2 - hormonal oral contraceptive use. The median of the menstrual fluid volume was 5.0 and the median number of cells was 5.2 × 106. Median of cell viability was 89.3%. After culture, mesenchymal stem cells increased from 0.031% of the total cells to 96.9%. The cells formed clusters and reached confluence after 15-21 days of culture in the first passage. In the second passage, clusters and the confluence were observed after 3 days of culture. No difference was observed between the groups. Our data suggest that oral hormonal contraceptive intake maintains the viability of mesenchymal stem cells from menstrual fluid.

Effects of oral contraceptive use on female sexual salivary hormones and indirect markers of muscle damage following eccentric cycling in women.

PURPOSE: To determine the effects of oral contraceptive (OC) use on salivary concentrations of testosterone, estrogen, progesterone, and its effects on the changes in indirect markers of muscle damage following eccentric cycling in women. METHODS: 10 oral contraceptive users at follicular phase (OC-FOL), 10 non-oral contraceptives users at follicular phase (NOC-FOL), and 10 non-oral contraceptives users at ovulation phase (NOC-OV) participated. Subjects performed 30 min of eccentric cycling at 90% of their maximal concentric power output (PO). Maximal voluntary isometric contraction (MVC), creatine kinase activity (CK), muscle soreness (SOR), and pain pressure threshold of vastus lateralis (PPT-VL) was assessed before, immediately after, and 24-96 h after cycling. Salivary estrogen, progesterone and testosterone concentrations were measured before, 72 and 96 h after exercise. RESULTS: No difference in estrogen levels between users and non-users was observed. Testosterone was 45% lower in OC-FOL than NOC-FOL at 96 h post-exercise (P = 0.01). Progesterone was 30.8-fold higher in NOC-OV than OC-FOL and 9.7-fold higher than NOC-FOL at 96 h post-exercise. The NOC-FOL recovered all indirect markers of muscle damage by 72 h post-exercise (P > 0.05). NOC-OV recovered MVC strength and muscle soreness (SOR and PPT-VL) by 96 h post-exercise (P > 0.05). OC-FOL did not recover baseline values of MVC, SOR, CK, and PPT-VL by 96 h. CONCLUSION: These results suggest that recovery after exercise-induced muscle damage took longer in OC-FOL, followed by NOC-OV and by NOC-FOL, respectively. Furthermore, testosterone and progesterone levels may affect recovery of indirect markers of muscle damage in women.