Design: Retrospective case series analysis, providing detailed insights into patient demographics, clinical courses, and biochemical profiles. The study encompasses a diverse range of treatment durations, spanning from 1 to 19 months, accompanied by a thorough review of existing literature on the topic.

Setting: An academic referral center dedicated to endometriosis care.

Patients or Participants: Ten women (mean age: 33 years) with diverse endometriosis phenotypes, received norethindrone for the treatment of endometriosis and subsequently developed transaminitis.

Interventions: Patients received norethindrone at 0.35 mg, 5 mg, and 10 mg daily. Monitoring involved serial liver function tests, imaging, and clinical evaluations.

Measurements and Main Results: Transaminitis was diagnosed in both asymptomatic and symptomatic patients, either during the work-up of acute symptoms or incidentally through routine lab tests, with varying initial AST:ALT ratios. Notably, all cases exhibited normalization of liver function tests after discontinuation, occurring within 1 to 12 months. Patients receiving higher dosages, such as 10 mg daily, demonstrated quicker resolution (average: 4 months). Reported adverse effects included nausea, vomiting, headache, rash, polyarthralgia, abnormal uterine bleeding (AUB), and dizziness. Complete resolution of transaminitis occurred upon discontinuation of norethindrone. Detailed patient profiles, including dosages, and biochemical parameters were analyzed. The time until resolution of transaminitis ranged from 1 to 12 months, accounting for different intervals of liver function testing.

Conclusion: Norethindrone-associated transaminitis is a rare but significant adverse event. The study underscores the importance of continuous monitoring of liver function, even in asymptomatic patients on norethindrone therapy. Vigilant management, including prompt discontinuation, consistently resulted in the resolution of transaminitis. Further investigations are imperative to fully comprehend progestin-mediated liver injury and identify specific groups susceptible to this adverse event.