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Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by periodic fever, serositis, and arthritis. In women, FMF attacks can sometimes be triggered by the menstrual cycle. Once diagnosed, prophylactic treatment with colchicine is generally recommended. Here, we report the case of a 34-year-old nulligravid Japanese woman who met the Tel-Hashomer criteria for FMF with menstruation-associated attacks and experienced a severe FMF episode following controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) without prophylactic colchicine. We also discuss management strategies for menstruation-associated FMF in patients who do not receive prophylactic therapy. Although prophylactic colchicine treatment was advised, the patient declined, and a plan for symptomatic management was established. She was referred to our clinic for infertility and subsequently underwent IVF due to endometriosis. At the initial examination, an increase in follicle-stimulating hormone (FSH) levels was observed, and endogenous endocrine function was regulated by administering estrogen and progestin. She experienced two withdrawal bleeding episodes without FMF attacks. Subsequently, COH using a gonadotropin-releasing hormone (GnRH) antagonist protocol was initiated, and oocyte retrieval was performed when her estradiol (E2) level reached 953 pg/mL. Immediately after the withdrawal bleeding following oocyte retrieval, she experienced her most severe FMF attack to date, presenting with fever above 38°C, diffuse abdominal pain, vomiting, and joint pain. To prevent further FMF attacks during the waiting period before embryo transfer, colchicine or dienogest was administered, effectively suppressing additional episodes. This case suggests that in patients with menstruation-associated FMF, withdrawal bleeding after COH may strongly provoke FMF attacks due to the abrupt decline in estrogen levels. It underscores the importance of prophylactic therapy with colchicine or other agents during assisted reproductive technology (ART). Furthermore, when prophylactic treatment is not feasible, alternative strategies such as fresh embryo transfer should be considered., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tatara et al.)

This longitudinal study investigated 1) differences in self-reported cycle-related symptom severity and recovery measures (sleep quality, readiness to train, resting heart rate) between pre-bleeding, bleeding, and non-bleeding days in athletes using/not using hormonal contraception (HC); 2) associations between symptom severity and recovery measures. Fifty-eight female endurance athletes recorded recovery measures, perceived symptom severity, and menstruation/withdrawal (bleeding) days for one year. Athletes were grouped as: intrauterine system (IUS)-, implant-, progestin-only oral contraceptive (POC)-, combined oral contraceptive (COC)- and non-HC users. All groups reported higher symptom severity during bleeding compared to pre-bleeding and non-bleeding days (both p  < .001), while implant users reported less severe symptoms than IUS ( p  < .001) and non-HC users ( p  = .008). Perceived sleep quality was lower during pre-bleeding compared to bleeding days ( p  < .001) for all groups. However, IUS users reported higher sleep quality ( p  = .039) and physical readiness-to-train ( p  = .010) than non-HC users. Symptom severity was negatively associated with sleep quality and physical readiness-to-train (both p  < .050). Pre-bleeding days and cycle-related symptom severity were found to negatively influence self-reported recovery measures in both HC- and non-HC users. Therefore, athletes and their support staff are advised to prioritize symptom management and the adjustment of recovery strategies on an individual basis throughout the athletes' cycles.

The usage of the oral contraceptive pill is widespread among athletes of various levels. However, there is limited knowledge on how the intake of the pill alters the submaximal and maximal endurance parameters between the oral contraceptive phases. Therefore, the aim of this study was to examine potential differences between the pill intake and withdrawal phase on endurance-related parameters in first-division handball players. In total, 15 female team handball players performed two graded exercise tests until volitional exhaustion on a motorized treadmill. Tests were performed during the pill intake (days 16-17) and withdrawal phase (day 2-3). Throughout the test, respiratory gases were measured breath-by-breath, and the heart rate was measured continuously. Before and after the graded exercise test, blood samples were obtained in order to assess the blood lactate concentration. Before each test, venous blood samples were taken to determine endogenous sex hormone levels. Ventilatory parameters ( V ˙ O 2 , V ˙ CO 2 , and V ˙ E, and respiratory equivalents for V ˙ O 2 and V ˙ CO 2 ) were measured, and the oxidation of fat and carbohydrates was calculated. A paired-sample t -test was used to assess differences between the two time points, and the significance was accepted as p < 0.050. Significant differences with lower values during the consumption phase were found for absolute (mean difference ± SD: 88 ± 131 mL∙min -1 ; p = 0.021) and relative V ˙ O 2peak (mean difference ± SD: 1 ± 2 mL∙min -1 ∙kg -1 ; p = 0.012). Higher values during the consumption phase were found for submaximal respiratory equivalents for V ˙ O 2 (mean difference ± SD: -1.1 ± 1.7; p = 0.028) and V ˙ CO 2 (mean difference ± SD: -0.9 ± 1.5; p = 0.032). No differences were found for all other parameters, including differences for endogenous sex hormones ( p > 0.050). The results of the current study suggest only marginal and physiologically insignificant differences in endurance-related parameters between oral contraceptive phases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mathy, Wessner, Haider, Tschan and Triska.)

Objective: To assess the clinical characteristics and endocrinological background of women with vascular retained products of conception (RPOC) after miscarriage or abortion and evaluate the effect of estrogen-progestogen therapy (EPT) as an initial treatment on this population based on their endocrinological background., Materials and Methods: Women with vascular RPOC after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (conjugated estrogen and norethisterone) were retrospectively reviewed. Their clinical characteristics, hormonal parameters, ultrasonographic findings, and outcomes were evaluated., Results: Of 35 women with vascular RPOC, 30 (86%) presented with vaginal bleeding at a visit, and 6 (17%) required inpatient management due to heavy bleeding. Among women who presented with vaginal bleeding, serum progesterone levels were significantly lower (0.25 vs. 6.5 ng/mL, p = 0.004) than those in women who did not present with vaginal bleeding. There were no differences in serum hCG levels (10.5 vs. 3.1 mIU/mL) or serum estradiol levels (65.4 vs. 162.3 pg/mL). After withdrawal bleeding following the first course of EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and 23 (66%) of all women had a thin and linear endometrium. All women could be treated by up to two courses of EPT and did not require additional interventions. The median duration to hCG normalization after the initial EPT was 24.5 (9-88) days., Conclusion: Women with vascular RPOC who have no bleeding had significantly higher levels of serum progesterone, indicating that administration of progestogen may have an effect on hemostasis. Endometrial bleeding can be prevented or stopped, and retained tissues can be conservatively expelled by oral administration of EPT, including norethisterone, in women with vascular RPOC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Oral contraceptive pills (OCP) are very popular in female athletes not only for contraceptive effects but also due to the possibility of cycle manipulation. Moreover, it is debatable whether the manipulation of the menstrual cycle has a beneficial effect on exercise performance. Therefore, the aim of this study was to investigate potential differences in knee-extensor and flexor strength performance of first division team sport athletes between phases of the oral contraceptive cycle. Sixteen female handball players (age: 23.3 ± 3.1 years; body mass: 67.0 ± 8.52 kg; body stature: 1.68 ± 0.05 m) using a monophasic OCP participated in strength performance tests, once during OCP consumption (CONS) and once during withdrawal (WITH). Tests were performed on a dynamometer to measure knee-extensor and flexor maximal voluntary isokinetic and isometric torque. Prior to each test, body mass was assessed, and venous blood samples were collected. Wilcoxon signed-rank test and magnitude-based inferences have been conducted to analyze differences between WITH and CONS. Significance was accepted at P < 0.05. No significant differences between oral contraceptive cycle phases of knee-extensor and flexor strength parameters and body mass have been indicated (all at P > 0.05). Follicle-stimulating hormone (FSH) ( P = 0.001) and luteinizing hormone ( P = 0.013) were significantly higher in WITH, whereby estradiol and progesterone showed no significant difference between phases (both at P > 0.05). These results support the notion that knee-extensor and flexor isokinetic and isometric strength performance does not differ between phases of oral contraceptive cycle in well-trained team sport athletes. OCP intake is suggested to cause a stable but downregulated hormone cycle, which has no effect on knee-extensor and flexor strength when comparing oral contraceptive cycle phases. Therefore, manipulation of the female cycle using OCP in order to achieve a higher knee-extensor and flexor strength performance does not seem to be justified; however, it is currently unclear if cycle manipulation might affect other physiological systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Reif, Wessner, Haider, Tschan and Triska.)

Our objective was to evaluate the safety and efficacy of direct initiation of gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients. Eighteen PCOS patients underwent ovulation induction with CC using a stair-step regimen. Patients who failed to respond to the maximal dose of CC initiated gonadotropin stimulation without inducing withdrawal bleeding, using the chronic low dose regimen. The primary outcome measure was the time to ovulation from the beginning of CC treatment until the day of ovulatory trigger. This was compared with the time to ovulation calculated according to the traditional approach, which includes inducing progesterone withdrawal bleeding between each CC dose increment and before gonadotropin therapy. The time to ovulation in the study group was 67.0 ± 6.8 days. The estimated time to ovulation according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy without prior induction of withdrawal bleeding in clomiphene resistant PCOS patients results in considerable reduction of the time to ovulation and is both safe and efficacious.

Objectives: To obtain more precise and detailed information regarding the bleeding patterns of nomegestrol acetate (NOMAC)/17β-estradiol (E2) and drospirenone/ethinyl estradiol (DRSP/EE) and to identify whether baseline demographic characteristics were associated with unscheduled bleeding, absent scheduled bleeding, or amenorrhea., Study Design: This analysis pooled results from two pivotal open-label, randomized trials that compared bleeding patterns of NOMAC/E2 and DRSP/EE. In the two studies 4317 women aged 18-50 years from 24 countries across the Americas, Europe, and Asia underwent treatment., Results: 2835 women taking NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen and 938 women taking DRSP/EE (3 mg/30 μg) in a 21/7-day regimen had at least 1 evaluable cycle for vaginal bleeding analyses. The frequency of absent scheduled bleeding was higher (p<.0001) for women using NOMAC/E2 than DRSP/EE across all 11 cycles (cycles 2-12), ranging between 17.6% and 31.6% and between 3.4% and 5.8%, respectively. For women who had absent scheduled bleeding in cycles 2, 3, or 4 the incidence of absent scheduled bleeding in subsequent cycles was high and ranged between approximately 50%-60% for NOMAC/E2 and approximately 40%-50% for DRSP/EE. Amenorrhea increased over time with both regimens, being higher with NOMAC/E2. Both absent scheduled bleeding and amenorrhea with NOMAC/E2 were more common in older women, overweight women, switchers, and smokers; unscheduled bleeding was more common in starters, but had no association with age, body mass index, and smoking., Conclusions: NOMAC/E2 is associated with a higher prevalence of absent scheduled bleeding compared with DRSP/EE. Absent scheduled bleeding and amenorrhea were associated with age, body weight, switching and smoking. Unscheduled bleeding was more common in starters., Implications: Information about the factors associated with bleeding patterns may help clinicians provide guidance to women considering use of the NOMAC/E2 oral contraceptive., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity., Objectives: To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs., Search Strategy: PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs., Selection Criteria: Articles assessing contraceptive efficacy or tolerability as the primary focus were included., Data Collection and Analysis: Abstracts of 319 articles were screened., Results: Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI., Conclusions: Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess whether continuous and extended regimens (CRs/ERs) of combined hormonal contraceptives (CHCs) improve symptoms related to withdrawal bleeding or the hormone-free interval and to compare the efficacy, safety, and cost of CRs/ERs to those of conventional 28-day regimens., Study Design: A literature search of the PubMed database was conducted for randomised clinical trials (RCTs) and observational studies published in any language between 2006 and 2013., Results: Sixteen RCTs and 14 observational studies evaluated issues related to our objectives. CRs/ERs, whose efficacy and safety were comparable to those described for conventional regimens, were preferred due to their improvement of symptoms related to withdrawal bleeding or the hormone-free interval and the lower costs resulting from the reduced incidence of these symptoms., Conclusion: The contraceptive efficacy and safety of CR/ER use of CHCs is at least equal to that of 28-days conventional regimens, and this use may have some cost savings. CRs/ERs are recommended for women willing to take a CHC for treatment of symptoms related to withdrawal bleeding or the hormone-free interval.