Deng Nianying, Zhong Jiayi, Deng Zhengjun, Chen Minling, Yan Liangqi, Li Haiting, Han Jiawei, Tao Enfu
Department of Pharmacy, Wenling Maternal and Child Health Care Hospital, Wenling, Zhejiang, China.
Department of Maternity, Wenling Maternal and Child Health Care Hospital, Wenling, Zhejiang, China.
Front Pharmacol. 2024 Jul 25;15:1404251. doi: 10.3389/fphar.2024.1404251. eCollection 2024.
Spironolactone, a potassium-sparing diuretic, is used to treat hypertension, heart failure, and certain hyperandrogenic disorders. Its use during pregnancy is not recommended due to the risk of feminizing male fetuses, primarily because of its antiandrogenic activity. However, human data remain scarce and largely inconclusive. Here, we present the first case of a 25-year-old pregnant woman, at 16 weeks of gestation, who was inadvertently exposed to spironolactone (240 mg/day) for 1 week due to a pharmacy dispensing error. The patient subsequently delivered a healthy male infant with normal genitalia at 38 weeks of gestation following vaginal delivery. Current follow-up shows that the infant is healthy and developing normally. This article summarizes the potential causes of spironolactone-induced anomalous genital development and explores the safety of new-generation mineralocorticoid receptor antagonists (MRAs) during pregnancy. The mechanisms behind spironolactone-induced anomalous genital development in male fetuses have not been fully elucidated. Spironolactone competes with dihydrotestosterone for binding to androgen receptors and inhibits enzymes involved in androgen biosynthesis, which may partly explain its antiandrogenic effects. Recent advancements in MRAs have led to the development of compounds with higher selectivity for the mineralocorticoid receptor, thereby reducing the incidence of antiandrogen side effects. These new-generation MRAs may be effective alternatives during pregnancy, but more data are needed to establish their safety in pregnant women. This case contributes to the limited but growing body of literature on the safety profile of spironolactone in pregnancy, providing insights into its effects during a critical period of fetal development.
螺内酯是一种保钾利尿剂，用于治疗高血压、心力衰竭和某些高雄激素血症疾病。由于存在使男性胎儿女性化的风险，主要是因其抗雄激素活性，故不建议在孕期使用。然而，相关人体数据仍然稀少且大多尚无定论。在此，我们报告首例病例，一名25岁孕妇，孕16周时因药房配药错误意外接触螺内酯（240毫克/天）达1周。该患者随后在孕38周经阴道分娩出一名生殖器正常的健康男婴。目前的随访显示该婴儿健康且发育正常。本文总结了螺内酯诱导生殖器发育异常的潜在原因，并探讨了新一代盐皮质激素受体拮抗剂（MRAs）在孕期的安全性。螺内酯诱导男性胎儿生殖器发育异常的机制尚未完全阐明。螺内酯与双氢睾酮竞争结合雄激素受体，并抑制参与雄激素生物合成的酶，这可能部分解释了其抗雄激素作用。MRAs的最新进展已导致开发出对盐皮质激素受体具有更高选择性的化合物，从而降低了抗雄激素副作用的发生率。这些新一代MRAs在孕期可能是有效的替代药物，但需要更多数据来确定其在孕妇中的安全性。该病例为关于螺内酯在孕期安全性的有限但不断增加的文献做出了贡献，为其在胎儿发育关键时期的影响提供了见解。
