Ethinylestradiol 30microgram / Norethisterone acetate 1.5mg tablets

Background: Relugolix, an oral GnRH receptor antagonist, is effective in treating uterine myomas and endometriosis. However, concerns persist regarding the venous thromboembolism (VTE) risk associated with its combination with oral estradiol (E2) and norethisterone acetate (NETA). Objective: This expert opinion evaluates the thrombotic risk of relugolix combined therapy (relugolix-CT) based on pharmacological data, clinical trials, and regulatory assessments. Methods: A review of pivotal trials (LIBERTY 1, LIBERTY 2, SPIRIT 1, SPIRIT 2), regulatory reports (European Medicines Agency, Food and Drug Administration), and real-world safety data was conducted, focusing on hemostatic effects and VTE risk. Results: Relugolix monotherapy reduces estrogen levels, leading to minor decreases in coagulation factors. While E2 and NETA mitigate hypoestrogenic effects, concerns about their prothrombotic potential remain. However, clinical trials and postmarketing surveillance have not shown a significant increase in VTE risk. A meta-analysis suggests that E2-based regimens have a lower thrombotic risk than ethinylestradiol-based therapies. Conclusion: The VTE risk of relugolix-CT appears lower than that of traditional combined oral contraceptives. Nonetheless, patient selection is essential, particularly for those with thrombotic risk factors. Continued real-world surveillance is crucial to refining its safety profile in clinical practice.

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Abnormal uterine bleeding (AUB) is a commonly presented gynaecological disorder that significantly affects the physical, emotional, and social well-being of a woman. Norethisterone acetate (NETA), a synthetic progestin, is widely utilized for managing AUB in view of its proven efficacy and favourable safety profile. Despite its extensive use, optimal dosing, duration, and patient-specific considerations in Indian women remain undefined. This expert opinion employed a two-pronged approach to assess the role of NETA in managing AUB in India. A comprehensive literature review was conducted to assess the evidence on efficacy, safety, pharmacokinetics, and formulation benefits, followed by four expert advisory board meetings held across India involving nearly 50 practicing experts. During expert advisory meetings, the current literature was discussed, and expert opinions were developed. The findings suggest that NETA is an effective option for stabilizing abnormal uterine bleeding, particularly during perimenopause, offering rapid symptom control, and well-tolerated and high patient satisfaction across multiple indications, including heavy menstrual bleeding, endometrial hyperplasia, and adenomyosis. Controlled-release formulations of NETA demonstrated pharmacokinetic equivalence to immediate-release regimens and comparable efficacy with the added advantage of improved adherence. Experts highlighted the importance of individualized dosing based on patient characteristics, such as body mass index, bleeding severity, and comorbidities.

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Objective: To review the real benefits of using combined oral contraceptives (COCs) containing natural hormones, also known as estradiol-containing COC (estradiol and estradiol valerate) in controlling abnormal uterine bleeding (AUB) compared to the already established data on treatment with combined pills containing ethinylestradiol (EE). Methods: Narrative review with analysis of studies published between 2010 and 2023, comparing the effects of EE and natural estrogen in the treatment of AUB, indexed in the PUBMED, WebOfScience, and Scielo databases. Results: A total of 342 articles were found in the selected databases. Of these, 235 articles were excluded because they were published before 2010 or lacked an explicit relationship with the topic; 107 articles were selected for title and abstract screening, of which 27 were fully read by the researchers, and 6 were included in the study. It was observed that the use of natural estrogens is effective in controlling abnormal uterine bleeding, often with fewer side effects and less cardiovascular and prothrombotic impact compared to ethinylestradiol (EE). However, some non-contraceptive benefits of EE, such as less water retention, improved skin oiliness, and acne, were not consistently observed with the use of natural estrogens. Conclusion: Estradiol-containing COC have proven to be effective in controlling AUB, in addition to reducing spotting and intermenstrual bleeding, with fewer undesirable side effects when compared to COCs with EE. On the other hand, COCs with estradiol and estradiol valerate less frequently present other non-contraceptive benefits.

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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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PURPOSE: to compare the effects of Dienogest 2 mg (D) alone or combined with estrogens (D + ethinylestradiol 0.03 mg, D + EE; D + estradiol valerate 1-3 mg, D + EV) in terms of symptoms and endometriotic lesions variations. METHODS: This retrospective study included symptomatic patients in reproductive age with ultrasound diagnosis of ovarian endometriomas. Medical therapy for at least 12 months with D, D + EE or D + EV was required. Women were evaluated at baseline visit (V1) and after 6 (V2) and 12 months (V3) of therapy. RESULTS: 297 patients were enrolled (156 in the D group, 58 in the D + EE group, 83 in the D + EV group). Medical treatment leaded to a significant reduction in size of endometriomas after 12 months, with no differences between the three groups. When comparing D and D + EE/D + EV groups, a significant decrease of dysmenorrhea was detected in the D group than in D + EE/D + EV group. Conversely, the reduction of dysuria was more significative in the D + EE/D + EV groups rather than in the D group. Regarding tolerability, treatment associated side effects were reported by 16.2% patients. The most frequent one was uterine bleeding/spotting, significantly higher in the D + EV group. CONCLUSION: Dienogest alone or associated with estrogens (EE/EV) seems to be equally effective in reducing endometriotic lesions mean diameter. The reduction of dysmenorrhea was more significative when D was administered alone, while dysuria seems to improve more when D is associated with estrogens.

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BACKGROUND: Cowden syndrome-associated endometrial carcinoma (CS-EC) is rare, and data on fertility-preserving treatment for young patients remain limited. This series describes the diagnosis and management of three patients with CS-EC who underwent fertility-sparing treatment. We also report the subsequent pregnancy outcome for one of these individuals. These cases provide a clinical reference for the individualized management of such patients. CASE PRESENTATION: Three patients (aged 29, 31, and 28 years) with germline Phosphatase and tensin homolog (PTEN) pathogenic variants and stage IA endometrial carcinoma underwent individualized fertility-sparing treatment. Case 1 (PTEN p.R189Qfs*9) failed levonorgestrel-releasing intrauterine system (LNG-IUS) treatment at 19 months. Eight cycles of GnRH agonist (GnRH-a) plus letrozole (LE) subsequently induced a complete response. A recurrence was successfully managed with twelve additional cycles of this regimen. Case 2 (PTEN p.R173C) attained remission after six months of megestrol acetate (MA). Case 3 (PTEN p.R335*) responded to MA over nine months, then developed complex mucinous papillary metaplasia during LNG-IUS maintenance, which resolved with ethinylestradiol/cyproterone acetate (EE/CPA). She subsequently conceived and delivered a live birth through Intracytoplasmic sperm injection (ICSI). During the follow-up period, all patients were administered maintenance therapy using a LNG-IUD. CONCLUSIONS: Fertility-sparing therapy may serve as a potentially feasible option for highly selected patients with stage IA CS-EC, and could lead to relatively favorable pregnancy outcomes. The clinical feasibility of this strategy relies heavily on strict patient selection, timely molecular diagnosis, and standardized continuous multidisciplinary management.

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