Amenorrhea secondary to vismodegib induced blockade of follicle stimulating hormone receptor activation
Vismodegib is a novel oral medication that targets the hedgehog pathway to treat basal cell carcinoma. Amenorrhea secondary to vismodegib is due to blockading of FSH-R signaling.
John Strasswimmer, M.D., Ph.D., Benjamin Latimer, B.S., Steven Ory, M.D.
Volume 102, Issue 2, Pages 555–557
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.
Main Outcome Measure(s):
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.
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