Ethinylestradiol 30microgram / Desogestrel 150microgram tablets

Background: Polycystic ovary disease (PCOD) is an endocrine disorder. It leads to menstrual disturbances, infertility, obesity and dermatological manifestations such as hirsutism and acne which leads to impaired health-related quality of life (QOL). Aims: To evaluate the perceived health related QOL in patients with PCOD treated with ethinyl oestradiol (35µg)/cyproterone acetate (2 mg) (EE/CPA) and ethinyl oestradiol (20 µg)/ desogestrel (0.15mg) (EE/DES) alone and in combination with low-dose metformin. Methods: A total of 117 patients with PCOD diagnosed according to Rotterdam Consensus Criteria 2003 with a hirsutism score of 8 or more according to modified Ferriman-Gallway Score (mFGS) were randomised to receive one of four drug combinations (arm A – EE/CPA, arm B- EE/DES, arm C- EE/CPA plus metformin, arm D- EE/DES plus metformin). The outcomes assessed were body mass index (BMI), hirsutism (using mFGS) and health-related QOL (Polycystic Ovary Syndrome Health- Related quality of life Questionnaire (PCOSQ) and a Visual Analog Scale (VAS) score) at baseline and 12 months after treatment. Results: PCOSQ score in relation to the hirsutism, emotions, menstruation, obesity, infertility and VAS score in relation to hirsutism and obesity had improved at the end of 12 months (p< 0.001) in all treatment arms. There was no difference between treatment arms in all measured outcomes at baseline and at the end of 12 months. Conclusion: Treatment with EE/CPA and EE/DES is associated with an improvement in perceived QOL in patients with PCOD. The addition of low-dose metformin did not have a significant benefit.

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OBJECTIVE: To assess the risk of intracranial meningioma associated with oral contraceptives containing desogestrel, levonorgestrel, or levonorgestrel combined with oestrogen. DESIGN: Case-control study. SETTING: French national health data system (Système National des Données de Santé). PARTICIPANTS: 8391 women living in France who required surgery for intracranial meningioma in 2020-23. Each patient was matched to 10 women without intracranial meningioma (controls) on year of birth and area of residence. MAIN OUTCOME MEASURE: Risk of intracranial meningioma associated with oral contraceptives containing desogestrel 75µg, levonorgestrel 30µg, or levonorgestrel 50-150 µg combined with oestrogen, and duration of use: short term use was defined by one or more dispensations within the year before the index date only, and prolonged use was defined by continuous use of one year or more (up to seven or more years of continuous use). Conditional logistic regression was used to calculate odds ratios. RESULTS: 1933 (2.3%)). In analyses of desogestrel according to duration of use, the odds ratio for risk of intracranial meningioma for short term use was 1.02 (95% confidence interval 0.77 to 1.34) and for prolonged use was 1.32 (1.14 to 1.53). Risk was driven by more than five continuous years of use: odds ratio 1.51 (1.17 to 1.94) for five to seven years and 2.09 (1.51 to 2.90) for ≥7 years. Excess risk was greater in women with meningiomas located in the middle or anterior part of the skull base (1.90 (1.47 to 2.46) and 1.50 (1.17 to 1.93), respectively) and in those who had previously used a progestogen of known associated increased risk (3.30 (2.64 to 4.11)). Results showed no excess risk of intracranial meningioma for levonorgestrel (alone or combined with oestrogen) regardless of duration of use. The estimated number needed to harm with desogestrel was 67 300 women for one intracranial meningioma requiring surgery. Risk was no longer observed one year after discontinuation of desogestrel. CONCLUSIONS: The results showed a small increased risk of intracranial meningioma in women who had used desogestrel 75 µg for more than five continuous years, but no risk in users of levonorgestrel (alone or combined with oestrogen).

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BACKGROUND: Melasma is a common hyperpigmentation disorder that causes significant distress to patients. In the real world, it is closely associated with various medications, making the timely identification and discontinuation of causative drugs an important aspect of clinical management. This study investigates the relationship between melasma and drug exposure based on data from the FDA Adverse Event Reporting System (FAERS) database. METHODS: This study includes reports from the first quarter of 2004 to the second quarter of 2024, focusing on cases related to melasma. We employed four statistical methods to analyze the association between suspected drugs and adverse events related to melasma. RESULTS: Within a specific timeframe, we extracted a total of 408 adverse reaction reports related to melasma. The result shows that a higher number of cases in female patients compared to male patients. The United States had the highest number of reported cases. We identified 22 drugs that were notably associated with melasma. Among these, the contraceptive "Ethinylestradiol and norethindrone" demonstrated the strongest signal of association. CONCLUSIONS: Melasma is associated with exposure to various medications, with a notable proportion of cases coincided with contraceptive use. The mechanisms involved include hormonal disturbances and oxidative stress.

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Importance: Hormonal contraceptives are widely used but how breast cancer risk differs by hormonal content remains unclear. Objective: To estimate the difference in breast cancer risk associated with different hormonal contraceptive formulations. Design, Setting, and Participants: This Swedish nationwide, population-based cohort study was conducted using linked national registers. All adolescent girls and women aged 13 to 49 years residing in Sweden as of January 1, 2006, with no history of breast cancer, ovarian cancer, cervical cancer, uterine cancer, bilateral oophorectomy, or infertility treatment were included and followed up from 2006 to 2019. Individuals were censored on meeting an exclusion criterion, reaching age 50 years, or study end, whichever occurred first. Data were analyzed from November 2023 to August 2025. Exposure: Ever use and duration of use of hormonal contraceptives, categorized by hormone formulations and route of administration. Main Outcomes and Measures: Time-dependent Cox regression was used to estimate hazard ratios (HRs) with 95% CIs for incident cases of in situ and invasive breast cancer. Results: Among 2 095 130 adolescent girls and women (median [IQR] age at diagnosis, 45 [41-48] years) who were followed up for 21 020 846 person-years, 16 385 breast cancer cases occurred. Ever use of any hormonal contraceptive was associated with increased breast cancer risk (HR, 1.24; 95% CI, 1.20-1.28), corresponding to 1 additional case per 7752 (95% CI, 5350-14 070) users, with both combined (HR, 1.12; 95% CI, 1.07-1.17) and progestin-only formulations (HR, 1.21; 95% CI, 1.17-1.25) being associated. Higher risk was associated with oral desogestrel-only formulations (HR, 1.18; 95% CI, 1.13-1.23) and oral desogestrel-combined formulations (HR, 1.19; 95% CI, 1.08-1.31), as well as implants containing etonogestrel, desogestrel's active metabolite (HR, 1.22; 95% CI, 1.11-1.35), compared to levonorgestrel-containing combined pills (HR, 1.09; 95% CI, 1.03-1.15) and levonorgestrel, 52 mg, intrauterine system (HR, 1.13; 95% CI, 1.09-1.18). No statistically significant increased risk was observed for medroxyprogesterone acetate injection, etonogestrel vaginal ring, or combined oral drospirenone, despite having many users. Conclusions and Relevance: Findings of this cohort study highlight that breast cancer risk varies substantially by progestin content in hormonal contraceptives, providing valuable insights to support more informed contraceptive prescription.

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To the Editor, We read with great interest the article of Ninivaggi et al. on activated protein C (APC) resistance induced by combined oral contraceptives (COCs) and would like to express our concerns regarding the ability of the thrombomodulin (TM)-based assay to more effectively discriminate between COC users and non-users.The authors stated that the type of progestin in COCs modulates the associated risk of thrombosis suggesting a higher risk of venous thromboembolism (VTE) with third generation COC containing desogestrel compared to second generation COC containing levonorgestrel. However, the actual risk depends primarily on the dose of ethinylestradiol (EE). For third-generation COCs, the VTE risk increases from 3.4 (95% CI, 2.5-4.6) to 4.3 (95% CI, 3.3-5.6) when EE dosage increases from 20 to 30 µg, while the dose of desogestrel remains constant. In contrast, for second-generation COCs, the VTE risk remains stable regardless of EE dose-2.2 (95% CI, 1.3-3.6) for EE 20 µg and 2.4 (95% CI, 1.8-3.2) for EE 30 µg-because EE and levonorgestrel doses increase proportionally. [1] These long-established epidemiological data, clearly show that the estrogenic component is the primary determinant of VTE risk, while the associated progestin modulates it to varying degrees. This debate is reminiscent of the misuse of the 'generation' term used following chronological order of appearance on the market and not based on any pharmacology basis. [2] Ignoring these differences leads to the assumption that all COCs confers the same VTE risk, which is certainly not the case. For instance, depending on the patient's coagulable status, a natural estrogen-based COC (which demonstrated a lower risk of VTE) may be appropriate whereas an EE-based COC would not be. [3] The aim of the study was to evaluate whether adding TM or APC to the thrombin generation (TG) assay results in differing sensitivity for detecting APC resistance in COC users. This rationale appears to stem from our 2021 review in Frontiers in Endocrinology [4], which raised considerations about the use of TM, APC, or both in assessing APC resistance. However, this interpretation is inaccurate, as our review does not discuss the methodology of the endogenous thrombin potential (ETP)-based APC resistance assay. Rather, it highlights the relevance of using a global sensitivity assay like the ETP-based APC resistance assay to determine a patient's coagulation status and support clinical decision-making when prescribing contraceptives.Briefly, the ETP-based APC resistance assay is based on the measurement of thrombin generation in presence and absence of a defined amount of exogenous APC. The endpoint of the test, which is the total amount of thrombin that has been generated over time, is quantitated by the ETP, which corresponds to the area under the thrombin generation curve. Results can be expressed as a percentage of inhibition, which reflects the decrease of the ETP-parameter between the two conditions, with and without APC. In other words, when targeting 90% inhibition with a reference plasma, this means that the ETP(+APC) is reduced by 90% compared to the ETP(-APC).The authors assert that TM is a better discriminator, but their results suggest otherwise. At the highest TM and inhibition was 86% for TM and only 73% for APC in non-users. This discrepancy highlights methodological limitations, especially regarding APC, as inhibition values near 90% were expected. The observed 73% inhibition with 5.5 nM APC suggests suboptimal dosing, which may reduce assay sensitivity. This could stem from their choice of pooled normal plasma to determine optimal TM and APC concentrations. Notably, the gender ratio of the pooled plasma is not reported, even though APC resistance levels vary between males and females, thereby influencing the assay's sensitivity. Despite this limitation, the absolute difference in inhibition % between non-users and COC users was higher using 5.5 nM APC than 15 nM TM (17% vs. 9%). Even at the lowest tested concentrations (1.5 nM APC vs. 2 nM TM), the difference remained higher for APC (21% vs. 14%). These findings are evident in Figure 3D, E andF The targeted 90% inhibition in a reference population is not chosen arbitrarily. By aiming for 90% inhibition, the assay operates near the plateau phase of the curve (x-axis, APC concentration; y-axis, inhibition%) [5], which helps minimize analytical variability. Indeed, variations in APC concentration will have limited impact on the inhibition %, as the slope of the curve is flatter. Conversely, targeting 50% inhibition corresponds to the steepest part of the curve, where even minor variation in APC activity can result in significant changes in the inhibition %.From a clinical perspective, by targeting 90% inhibition in a normal population, it allows for a greater sensitivity to the various estro-progestin association, since the level of APC resistance can fluctuate across a range from 0 to 90% whereas this range is halved when aiming for 50% inhibition. Ultimately, targeting 90% inhibition provides greater analytical precision and enhanced clinical sensitivity.For now, there is no available commercial kit for the intended purpose of assessing the thrombotic risk of women using COC. Solely, the methodology for the ETP-based APC resistance assay has been validated and standardized according to FDA and ICH guidelines. In this validated methodology, reagents (STG ThromboScreen®, Thrombin calibrator® , FluCa Kit®) -including APC originally from Enzyme Research Laboratory -are supplied by Diagnostica Stago, ensuring reliable and consistent availability. Indeed, an important aspect of a validated technology is the ability of providing reproducible results over time. In other words, batch changes must be properly controlled and fully documented. The use of home-made methodologies, as performed by Ninivaggi et al. fails to meet the standard of analytical rigor as outlined above.Over the past 30 years, many studies have explored the effects of COC on hemostasis. Regarding the protein Cprotein S anticoagulant pathway, increases in protein C and decreases in protein S levels have been described. [6]. When exogenous TM is used, the patient endogenous protein C is activated, and then associates with endogenous protein S to inactivate FVa and then FVIIIa. In women using COC, the decrease of protein S could be,

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Statistics from 2024 have shown that 50% of young women use contraception. Nowadays, it is not only used to prevent pregnancy. Positive effects of this treatment can be seen in cases of acne vulgaris, hirsutism, and painful menstruation. A controversial topic is the use of combined oral contraception (COC) in women with migraine with aura - it is contraindicated, but for headaches associated with the menstrual cycle, there is a chance of improvement, especially with the 28/0 regimen. This review assessed differences in the effects of substances contained in COC. Tablets containing ethinylestradiol in combination with drospirenone, levonorgestrel, desogestrel, chlormadinone acetate, dienogest, or lynestrenol were compared. The effects of different drug doses on body mass index (BMI), blood pressure, and the severity of adverse effects in women were considered. An individualized approach to patients is important to select COCs appropriate for the condition and at the same time minimize adverse effects, thereby improving quality of life. The progress in the development of newer COCs, such as an estetrol-containing pill with drospirenone, is promising as well.

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The WHO aims to reduce iron deficiency anaemia globally. Use of modern hormonal contraception (HC) could offer protection against anaemia in premenopausal women, but population-level effectiveness is unclear. We aim to quantify the effect of HC on anaemia. This nested case-control study includes over half the fertile-aged female population of Finland in 2017. Data on HC use from the national Prescription Center were combined with data on anaemia diagnosis from national care registries. Cases (anaemia diagnosis during follow-up, 2019-2020) were matched with up to five controls by age and municipality. After calculating the minimally sufficient adjustment set, adjusted odds ratios were derived in a conditional multivariable regression model accounting for matching. 3 100 cases of anaemia were matched with 13 143 controls. The minimally sufficient adjustment set included age, education level, obesity, abnormal uterine bleeding, and cancer. Compared to non-users of HC, risk of anaemia was lower in users of combined oral contraceptives containing ethinylestradiol (0·74 [0·66-0·83]) or oestradiol (0·49 [0·35-0·68]), progestin-only oral contraceptives (0·42 [0·35-0·51]), LNG-IUDs (0·64 [0·43-0·94]), and contraceptive vaginal rings (0·68 [0·49-0·94]). Individual product effects ranged from 0·77 [0·66-0·90] for drospirenone and ethinylestradiol to 0·40 [0·32-0·48] for desogestrel-only. Benefits of HC use extend to anaemia protection on population level. Anaemia protection should be included in guidelines on HC to support clinical decision making.

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The aim was to investigate the adverse event reporting patterns of 2 commonly used combined contraceptives (desogestrel/ethinyl estradiol (DES) and norethisterone/ethinyl estradiol (NOR)) using the Food and Drug Administration Adverse Event Reporting System database. We selected data from the first quarter of 2004 to the second quarter of 2024 from the Food and Drug Administration Adverse Event Reporting System database for disproportionate analysis. We performed signal detection and comparative analysis using the reporting odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean for adverse events (AEs) related to DES, and NOR. From January 1, 2004 to June 30, 2024, a total of 35,83,091 reports related to drug AEs were extracted. Among these, 1177 reports were associated with DES, involving 4057 AEs; 1677 reports were associated with NOR, involving 4353 AEs. In the category of reproductive system and breast disorders, the reporting association for abnormal withdrawal bleeding was stronger for DES, while withdrawal bleeding and hypomenorrhoea were more frequently reported with NOR. In pregnancy, puerperium, and perinatal conditions, signals for complications of delivery and labor were more prominent in patients using DES. Conversely, NOR showed stronger associations with reports of contraceptive failure (pregnancy during oral contraceptive use and pregnancy while using contraceptives). In vascular disorders, vena cava thrombosis and splenic infarction were reported more frequently in patients using NOR, while arterial thrombosis and embolism were more commonly reported in those using DES. Subgroup analyses showed that women aged 18 to 40 years had a greater number of preferred terms and signal strength in the aforementioned 3 major systems. In this analysis, DES showed stronger reporting signals for arterial thrombosis, perinatal complications, and abnormal withdrawal bleeding, while NOR was more associated with vena cava thrombosis, contraceptive failure, withdrawal bleeding, and breast enlargement. Clinicians may pay particular attention to women of reproductive age, specifically those aged 18 to 40 years.

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