Influence of Oral Contraceptives on Lipid Profile and Trajectories in Healthy Adolescents-Data From the EVA-Tyrol Study.

PURPOSE: Oral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. METHODS: Lipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. RESULTS: For this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. DISCUSSION: We showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors.

Acceptability of an on-demand pericoital oral contraceptive pill: a systematic scoping review.

BACKGROUND: Access to an on-demand pericoital oral contraceptive pill - used to prevent pregnancy within a defined window around sexual intercourse - could offer women more reproductive agency. A contraceptive with this indication is not currently available in any market. This review aims to understand international user appeal for an on-demand pericoital oral contraceptive pill. METHODS: Systematic scoping review, comprising 30 peer-reviewed papers published between 2014-2023. RESULTS: Data from 30 papers reporting on research from 16 countries across five World Health Organisation regions suggests widespread user appeal for on-demand oral contraceptive pills that can be used peri- or post-coitally, especially among women who are younger, more educated or who have less frequent sex. Women of varying age, wealth, employment or relationship status, and with different prior experience of using modern contraceptives, were also interested. Women identified clear rationale for use and preference of these types of product: close alignment with women's sexual lives that comprised unplanned, spontaneous or occasional sex; perceived convenience and effectiveness; discreet use of pills to negotiate contextual circumstances that constrained their reproductive agency. Factors inhibiting use included knowledge barriers and attitudes of service providers, a lack of knowledge and misinformation among end-users, women's dislike of menstrual side effects and myths related to the effects of hormone content on future fertility. CONCLUSIONS: Introduction of an on-demand pericoital oral contraceptive pill could expand contraceptive choice for diverse women experiencing unmet need for modern contraception and constrained sexual and reproductive agency. Priorities for future research include: broadening the geographical scope of evidence to include SE Asia and the Pacific, and international rural and peri-urban settings; documenting the perspectives of adolescents and unmarried young people; identifying opportunities for innovation in the supply channels to enhance appropriate, affordable access to on-demand oral contraceptives; and unpacking how to bring new pericoital contraceptives to the market in a variety of international settings.

Access to an oral contraceptive pill that is used as needed to prevent pregnancy and taken within a defined window around sexual intercourse (i.e. an on-demand pericoital oral contraceptive pill) could offer women more reproductive agency. Though not currently available in any market, our analysis from this review of international literature reveals widespread appeal among women for using this type of contraceptive product. Clear rationale supporting use and preference included: (1) closer alignment with women's sexual lives that comprised desired but unplanned, spontaneous or occasional sex than other contraceptives; (2) perceived convenience and effectiveness, offering benefits over other modern contraceptives; and (3) women feeling able to overcome social values and beliefs that constrained their reproductive agency. There were also barriers to use of this type of product, including knowledge gaps and attitudes of service providers, a lack of knowledge and misinformation among end-users, women's dislike of the side effects, and myths and misconceptions about the impact of the hormone content in pills on future fertility. Introduction of an on-demand pericoital oral contraceptive pill could expand contraceptive choice for diverse women experiencing unmet need for modern contraception and constrained sexual and reproductive agency. Priorities for future research include: broadening the geographical scope of evidence to include SE Asia and the Pacific, and rural and peri-urban settings; documenting the perspectives of adolescents and unmarried young people; identifying opportunities for innovation in the supply channels to enhance appropriate, affordable access to this type of contraceptive; and unpacking how to bring this new contraceptive to the market in a variety of international settings.

A bitter pill to swallow: adjustments to oral contraceptive pill use in polycystic ovary syndrome.

INTRODUCTION: This Special Report aims to highlight the importance of tailored therapies in women with Polycystic Ovary Syndrome (PCOS), avoiding prescribing generalized or unsuitable therapies based on oral contraceptive pills (OCPs). AREAS COVERED: This article discusses the benefits and risks of OCP-based therapy, highlighting the possible undesirable effects, especially in those patients exhibiting risk factors as women with PCOS, and the importance of carefully evaluated tailored therapeutic approaches. Literature searches were performed with the use of PubMed, Google Scholar, and Web of Science between January and February 2024. EXPERT OPINION: Considering the recent re-analysis of PCOS Rotterdam Criteria by the Expert Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), the traditional Rotterdam phenotypes can be reclassified to achieve more efficacious therapy choices. Using personalized therapies that consider the specific clinical characteristics of the patient allows to improve the management of the syndrome, thus avoiding the generalized use of OCPs, which risk treating only symptoms of PCOS rather than the underlying cause. In cases when contraceptive purpose is desired, patients may benefit from combined therapy with diet or insulin-sensitizer agents, as inositol, to rebalance the metabolic profile, thus reducing the risk of developing future complications.

Gene-Environment Interaction Between CYP1B1 and Oral Contraception on Frontal Fibrosing Alopecia.

Importance: Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, ST3GAL1, and SEMA4B. However, CYP1B1, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A>G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies. Objective: To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in CYP1B1 (c.1358A>G, p.Asn453Ser) on FFA risk. Design, Setting, and Participants: This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023. Main Outcome and Measure: The main outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model. Results: Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34 254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31 177 (91.0%). An association between female FFA and the CYP1B1 risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; P = 8.41 × 10-8) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; P = .39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P = .02). Conclusions and Relevance: This gene-environment interaction analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of CYP1B1 was associated with increased odds of FFA only in participants with OCP history.

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments.

Introduction: Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers. Materials and methods: Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a post hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls. Results: Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively). Conclusion: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. Clinical Trial Registration: https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.

Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women.

Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 µg/250 µg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 µg) EE (n = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 µg, Cycles 1-2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3-4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, n = 16; AE [deemed unelated to GLE/PIB], n = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.