gdc-0449 and Amenorrhea

To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib.. Case report and literature review.. Academic and private dermatology and fertility practices.. A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib.. Physical examination and endocrine evaluation.. Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone.. FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Müllerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy.. 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.

Topics: Adult; Amenorrhea; Anilides; Anti-Mullerian Hormone; Antineoplastic Agents; Biomarkers; Carcinoma, Basal Cell; Estrogens; Female; Follicle Stimulating Hormone, Human; Humans; Menstruation; Primary Ovarian Insufficiency; Pyridines; Receptors, FSH; Recovery of Function; Skin Neoplasms; Time Factors; Treatment Outcome

Topics: Amenorrhea; Anilides; Basal Cell Nevus Syndrome; Female; Humans; Pyridines