title: 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.
  
  
  METHODS
  Case report and literature review.
  
  
  METHODS
  Academic and private dermatology and fertility practices.
  
  
  METHODS
  A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib.
  
  
  METHODS
  Physical examination and endocrine evaluation.
  
  
  METHODS
  Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Melanoma and Cutaneous Oncology Program, Lynn Cancer Institute, Boca Raton Regional Hospital, Boca Raton, Florida; Department of Biochemistry, Florida Atlantic University, Boca Raton, Florida; Dermatology Associates of the Palm Beaches, Delray Beach, Florida. Electronic address: strasswimmer@gmail.com.
authors.forename: John
authors.initials: J
authors.lastname: Strasswimmer
authors.affiliation: Dermatology Associates of the Palm Beaches, Delray Beach, Florida.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Latimer
authors.affiliation: IVF Florida, Margate, Florida; Department of Obstetrics and Gynecology, Florida International University, Miami, Florida.
authors.forename: Steven
authors.initials: S
authors.lastname: Ory
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D000813:Anilides / Q000009:adverse effects*; D054304:Anti-Mullerian Hormone / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004967:Estrogens / Q000097:blood; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D006801:Humans; D008598:Menstruation / Q000187:drug effects*; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011725:Pyridines / Q000009:adverse effects*; D011962:Receptors, FSH / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020127:Recovery of Function; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D015415:Biomarkers; D004967:Estrogens; D043373:Follicle Stimulating Hormone, Human; C538724:HhAntag691; D011725:Pyridines; D011962:Receptors, FSH; D054304:Anti-Mullerian Hormone
keywords: BCC; FSH-R; Vismodegib; amenorrhea; hedgehog