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.

Like Comment

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. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

No comments yet.