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

Fertil Steril. 2014 Aug;102(2):555-7. doi: 10.1016/j.fertnstert.2014.04.045. Epub 2014 Jun 2.


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.

Keywords: BCC; FSH-R; Vismodegib; amenorrhea; hedgehog.

Publication types

  • Case Reports
  • Review

MeSH terms

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


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