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.

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Authors

John Strasswimmer, M.D., Ph.D., Benjamin Latimer, B.S., Steven Ory, M.D.

Volume 102, Issue 2, Pages 555–557

Abstract

Objective:

To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib.

Design:

Case report and literature review.

Setting:

Academic and private dermatology and fertility practices.

Patient(s):

A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib.

Intervention(s):

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.

Result(s):

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.

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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00405-1/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.