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

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.

• Authors: John Strasswimmer, Benjamin Latimer, Steven Ory
• Journal: Fertility and sterility (Fertil Steril) Vol. 102 Issue 2 Pg. 555-7 (Aug 2014) ISSN: 1556-5653 [Electronic] United States
• PMID: 24890268 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anilides
• Antineoplastic Agents
• Biomarkers
• Estrogens
• Follicle Stimulating Hormone, Human
• HhAntag691
• Pyridines
• Receptors, FSH
• Anti-Mullerian Hormone

Topics

• Adult
• Amenorrhea (blood, chemically induced, metabolism, physiopathology)
• Anilides (adverse effects)
• Anti-Mullerian Hormone (blood)
• Antineoplastic Agents (adverse effects)
• Biomarkers (blood)
• Carcinoma, Basal Cell (drug therapy, metabolism, pathology)
• Estrogens (blood)
• Female
• Follicle Stimulating Hormone, Human (blood)
• Humans
• Menstruation (drug effects)
• Primary Ovarian Insufficiency (blood, chemically induced, metabolism, physiopathology)
• Pyridines (adverse effects)
• Receptors, FSH (antagonists & inhibitors, metabolism)
• Recovery of Function
• Skin Neoplasms (drug therapy, metabolism, pathology)
• Time Factors
• Treatment Outcome