BACKGROUND: Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic.
METHODS: Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 μg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days.
RESULTS: The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks - 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD.
CONCLUSIONS: The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible.
BACKGROUND: Clinical trials.gov NCT04007874 . Registered 28 June 2019.

Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor overall survival, with only 30% of patients surviving for longer than 5 years after diagnosis. The reason for this poor outcome includes late diagnosis due to non-specific symptoms and a lack of any highly effective biomarkers of the early stages of ovarian carcinogenesis. However, it is important to note that some modifiable lifestyle factors can be preventative [pregnancy, breastfeeding and combined oral contraceptives pill (COCP) use].
There is now increasing data reporting the role of epigenetic changes, which are detectable in ovarian cancer tumors, suggesting the possibility that epigenetics may also play a key role in the mechanism of long-term effective prevention of ovarian cancer. To our knowledge, there is a lack of high-quality data on the molecular mechanisms of ovarian cancer prevention, although several hypotheses have been proposed.
This review focusses on the evidence for a proposed novel hypothesis-that COCPs act as a chemoprevention through the impact on the epigenome of the cells of origin of ovarian cancer-fallopian tubes epithelium.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women.
OBJECTIVE: As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin, and combination treatment were evaluated.
METHODS: Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL were searched.
METHODS: Women with PCOS included in randomized controlled trials (RCTs).
METHODS: We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed.
RESULTS: The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08; 95% CI 4.81, 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/L; 95% CI -174.46, -62.75) and testosterone (0.48 nmol/L; 95% CI 0.32, 0.64) compared with COCP. COCP was inferior for FAI (0.58; 95% CI 0.36, 0.80) and SHBG (-16.61 nmol/L; 95% CI -28.51, -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/L; 95% CI -40.65, -13.59) and triglycerides (-0.15 mmol/L; 95% CI -0.29, -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/L; 95% CI 7.79, 26.26) and insulin resistance (0.44; 95% CI 0.17, 0.70) compared with combination treatment.
CONCLUSIONS: The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).

Since its introduction in 1960, the combined oral contraceptive pill has become the dominant reversible contraceptive technology for controlling female fertility in spite of early and ongoing ethical, critical medical, and societal disapproval. Over the last decade, prescription rates among young women in Western Europe have declined alongside the rise of social media use. This article investigates the mechanisms underlying this change in contraceptive choices and the role played by social media in this trend. Via exploratory online observation and an in-depth interview study with 19 informants in Germany and Denmark, we find social media consolidates the social construction of hazards associated with the contraceptive pill by reshaping young women\'s risk perception from questions around drug reliability and safety to those of individual physical, mental, and social well-being. We shed light on how social media contributes to the delegitimation of health professionals such as gynaecologists and general practitioners and adds to wider debates on the erosion of medical authority and the attendant rise of peer influencers. We condense our findings into a framework for health-related attitude formation and decision-making in the social media age, which elucidates how social media amplifies and reshapes societal discourses regarding health-related technologies, choices, and risks.

The combined oral contraceptive (COC) pill is often employed to address physical and neurological symptoms in menstrual cycle-related disorders by suppressing shifts in endogenous gonadal hormone fluctuations. Symptom persistence, especially in the lead up to the hormone-free interval (HFI), suggests an underlying neurobiological mechanism of preserved cycling. Our study utilised a non-invasive method of visually inducing long-term potentiation (LTP) to index changes in neural plasticity in the absence of hormonal fluctuations.
Visually induced LTP was recorded using electroencephalography in 24 healthy female COC users across three sessions: days 3 and 21 during active hormone pills, and day 24 during the HFI. The Daily Record of the Severity of Problems (DRSP) questionnaire tracked premenstrual symptoms. Dynamic causal modelling (DCM) was used to elucidate the neural connectivity and receptor activity changes associated with LTP across different days of COC.
Visually induced LTP was greater on day 21 than day 3 (p = 0.011) and was localised to the P2 visually evoked potential. There was no effect of the HFI (day 24) on LTP. DCM of differences between days 3 and 21 showed changes to inhibitory interneuronal gating of LTP in cortical layer VI. The DRSP only showed a significant increase in symptoms in the HFI, meaning the LTP result appeared more sensitive to cyclicity.
This study provides objective evidence of preserved cyclicity in COC users through enhanced LTP on day 21 compared to day 3 of a 28-day COC regimen, indicating that relatively higher excitation in the brain despite peripheral gonadal suppression may underlie and exacerbate menstrual cycle-related disorders.

To determine how the contraceptive-specific serum antimüllerian hormone (AMH) levels compare across ages and percentiles in a reproductive-age cohort.
Cross-sectional analysis of a prospectively recruited cohort.
Community.
This study included US-based women of reproductive age who purchased a fertility hormone test and consented to participate in research between May 2018 and November 2021. At the time of hormone testing, participants were users of various contraceptives (combined oral contraceptive [n = 6,850], progestin-only pill [n = 465], hormonal [n = 4,867] or copper [n = 1,268] intrauterine device, implant [n = 834], vaginal ring [n = 886]) or women with regular menstrual cycles (n = 27,514).
Contraceptive use.
Age and contraceptive-specific estimates of AMH.
There were contraceptive-specific effects on AMH with effect estimates ranging from 0.83 (95% confidence interval [CI], 0.82-0.85) (17% lower) for the combined oral contraceptive pill to no effect (1.00; 95% CI, 0.98-1.03) for the hormonal intrauterine device. We did not observe age-specific differences in suppression. However, there were differential suppressive effects of the contraceptive method across AMH percentiles, with the greatest effect at lower percentiles and least effect at higher percentiles. For example, for women taking the combined oral contraceptive pill, the AMH level was 32% lower at the 10th percentile (coefficient, 0.68; 95% CI, 0.65-0.71), 19% lower at the 50th percentile (coefficient, 0.81; 95% CI, 0.79-0.84), and 5% lower at the 90th percentile (coefficient, 0.95; 95% CI, 0.92-0.98), with other forms of contraception showing similar discordances.
These findings reinforce the body of literature that shows that hormonal contraceptives have different impacts on the AMH levels at a population level. These results add to this literature that these effects are not consistent; instead, the greatest impact occurs at the lower AMH percentiles. However, these contraceptive-dependent differences are small compared with the known biological variability in ovarian reserve at any given age. These reference values enable robust assessment of an individual\'s ovarian reserve relative to their peers without requiring cessation or potentially invasive removal of contraception.

Limited recent observational data have suggested that there may be a protective effect of oestrogen on the severity of COVID-19 disease. Our aim was to investigate the association between hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP) use and the likelihood of death in women with COVID-19.
We undertook a retrospective cohort study using routinely collected computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. We identified a cohort of 1,863,478 women over 18 years of age from 465 general practices in England. Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use and all-cause mortality among women diagnosed with confirmed or suspected COVID-19 in unadjusted and adjusted models.
There were 5,451 COVID-19 cases within the cohort. HRT was associated with a reduction in all-cause mortality in COVID-19 (adjusted OR 0.22, 95% CI 0.05 to 0.94). There were no reported events for all-cause mortality in women prescribed COCPs. This prevented further examination of the impact of COCP.
We found that HRT prescription within 6 months of a recorded diagnosis of COVID-19 infection was associated with a reduction in all-cause mortality. Further work is needed in larger cohorts to examine the association of COCP in COVID-19, and to further investigate the hypothesis that oestrogens may contribute a protective effect against COVID-19 severity.

OBJECTIVE: To compare the effects of dienogest and a combined oral contraceptive pill (COCP) after laparoscopic surgery on pain and quality of life in women with severe endometriosis.
METHODS: A randomized double-blind pilot study was conducted from March 2018 to March 2020 in women with severe endometriosis confirmed by laparoscopic surgery. A total of 108 patients who had undergone laparoscopic surgery received dienogest, COCP, or placebo daily for 6 months. Primary and secondary outcomes were compared between the three groups.
RESULTS: Treatment with dienogest or COCP was associated with improved self-reported pain after 6 months of treatment, as evidenced by significantly lower scores for pelvic pain and dyspareunia compared with placebo (P < 0.05). Significant differences in overall quality of life score were observed over 6 months in the dienogest, COCP, and placebo groups (mean difference 22.00, 23.45, and 6.45 points, respectively; P < 0.001). Post-hoc analysis revealed a significant difference in overall quality of life score between the placebo group and the dienogest (P < 0.001) and COCP groups (P = 0.004).
CONCLUSIONS: Postoperative administration of dienogest or COCP reduced endometriosis-associated pain and improved quality of life in women with severe endometriosis.
BACKGROUND: https://en.irct.ir/trial/43070.

Determine the associations between factors and sexual practices and the composition of the vaginal microbiome (VM) of women treated for bacterial vaginosis (BV).
Prospective cohort study.
The Melbourne Sexual Health Centre, Melbourne, Australia.
Seventy-five reproductive-age women diagnosed with clinical BV, treated with first-line antibiotics and followed for up to 6 months.
Women self-collected vaginal swabs and completed questionnaires at enrolment, the day following antibiotics and monthly for up to 6months until BV recurrence or no BV recurrence (n = 430 specimens). Bacterial composition was determined using 16S rRNA gene amplicon sequencing. The effects of ongoing factors on VM composition (utilising 291 monthly specimens) were assessed using generalised estimating equations population-averaged models, which accounted for repeated measures within individuals.
The relative abundance of vaginal bacterial taxa.
Women who reported ongoing sex with a regular sexual partner (RSP) had a VM comprised of increased relative abundance of non-optimal BV-associated bacteria (Adjusted co-efficient [Adjusted co-eff] = 11.91, 95% CI 3.39to20.43, P = 0.006) and a decreased relative abundance of optimal, Lactobacillus species (Adjusted co-eff = -12.76, 95% CI -23.03 to -2.49, P = 0.015). A history of BV was also associated with a decreased relative abundance of Lactobacillus spp. (Adjusted co-eff = -12.35, 95% CI -22.68, P = 0.019). The relative abundance of Gardnerella, Atopobium and Sneathia spp. increased following sex with an RSP.
Sex with an untreated RSP after BV treatment was associated with a VM comprised of non-optimal BV-associated bacteria. BV treatment approaches may need to include partner treatment if they are to achieve a sustained optimal VM associated with improved health outcomes.
Sex drives a return to a \'non-optimal\' vaginal microbiota after antibiotics for bacterial vaginosis.

OBJECTIVE: To compare the efficacy and safety of dienogest with combined oral contraceptives (COCs) for treating adenomyosis-associated symptoms.
METHODS: This was a randomized clinical trial including women with symptomatic adenomyosis conducted from March 1, 2019 to August 1, 2020 at Assiut Woman\'s Health Hospital, Egypt. Participants were randomly assigned to the dienogest group or COCs group. The primary outcome was the level of adenomyosis-associated pain from before to 6 months after treatment measured by a visual analog scale (VAS). Changes in the uterine bleeding pattern, uterine volume, and uterine artery blood flow were also reported.
RESULTS: The VAS score of pain was significantly decreased in both groups; however, the decreased rate was more pronounced in the dienogest group (3.21 ± 1.18) in comparison with the COCs group (4.92 ± 1.22). Bleeding pattern was improved greatly; uterine volume and uterine artery blood flow decreased significantly in the dienogest group. However, women in the dienogest group reported a higher rate of side effects.
CONCLUSIONS: Dienogest and COCs are effective in treating adenomyosis-associated symptoms after 6 months of use but dienogest is more effective. The decrease in uterine volume and uterine artery blood flow may be the cause of the treatment effect. Dienogest carries a higher risk of side effects.
BACKGROUND: gov: NCT03890042.