Amenorrhea secondary to a vismodegib-induced blockade of follicle-stimulating hormone-receptor activation

作者：Strasswimmer John^*; Latimer Benjamin; Ory Steven

来源：Fertility and Sterility, 2014, 102(2): 555-557.

DOI：10.1016/j.fertnstert.2014.04.045

• Vismodegib
• FSH-R
• amenorrhea
• BCC
• hedgehog

Objective: To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. %26lt;br%26gt;Design: Case report and literature review. %26lt;br%26gt;Setting: Academic and private dermatology and fertility practices. %26lt;br%26gt;Patient(s): A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib. %26lt;br%26gt;Intervention(s): Physical examination and endocrine evaluation. %26lt;br%26gt;Main Outcome Measure(s): Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Mullerian hormone. %26lt;br%26gt;Result(s): FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Mullerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy. %26lt;br%26gt;Conclusion(s): Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway is indicated for advanced basal cell carcinoma and is associated with amenorrhea. The mechanism is unknown; it has some features of ovarian failure but preserves ovarian potential through blockading of FSH-receptor-dependent signal transduction. This effect appears to be rapidly reversible upon cessation of therapy. Vismodegib and related compounds may have potential for a role in intervention for gynecologic and endocrine disorders and in therapy for other issues involving FSH-dependent function.

• 出版日期2014-8