title: A Randomized Prospective Double-Blind Comparison Trial of Clomiphene Citrate and Anastrozole in Raising Testosterone in Hypogonadal Infertile Men.
abstract: OBJECTIVE
  Clomiphene citrate (CC) and anastrozole (AZ) have been used off label to increase testosterone (T) in hypogonadal infertile men (HIM). Both medications have been shown to increase T with different effects on estradiol (E2) and T-to-E2 ratios. There are no reported randomized trials comparing CC and AZ to improve T levels in HIM. We aimed to establish equivalence of CC vs. AZ with respect to improvement in T levels in HIM.
  
  
  METHODS
  We randomized 26 HIM (T less than 350 ng/dL and normal luteinizing hormone [LH]). Patients were randomized to CC (25 mg/day) or AZ (1 mg/day) for 12 weeks. Hormones assayed were total T, free T, E2, LH, follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG). Patient-reported outcomes were the International Index of Erectile Function, Erection Hardness Scale, and the Androgen Deficiency in the Aging Male questionnaires. Blood tests and questionnaires were recorded at baseline, 6 and 12 weeks. Semen analyses were performed at baseline and 12 weeks.
  
  
  RESULTS
  T increased significantly from baseline in both groups at 6 and 12 weeks. There was a significantly larger increase in T and mean increase from baseline in CC vs. AZ (571 vs. 408 ng/dL, respectively). Whereas E-2 levels increased in the CC group, they decreased in the AZ group. Though both groups demonstrated an increase in T-to-E-2 ratio from baseline, statistic significance at 6 and 12 weeks was only achieved with AZ. Neither group demonstrated significant changes in seminal parameters or patient-reported outcomes.
  
  
  CONCLUSIONS
  We failed to demonstrate equivalence of CC vs. AZ. CC resulted in significantly higher T levels than AZ. AZ resulted in a significantly larger increase in T/E-2 ratio than CC. No significant differences between CC and AZ on seminal parameters or patient-reported outcomes were demonstrated.
authors.affiliation: Albany Medical Center, Division of Urology, Albany, NY, USA.
authors.forename: Sevann
authors.initials: S
authors.lastname: Helo
authors.affiliation: Albany Medical Center, Division of Urology, Albany, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ellen
authors.affiliation: Urology Associates of Central Missouri, Columbia, MO, USA.
authors.forename: Clay
authors.initials: C
authors.lastname: Mechlin
authors.affiliation: Albany Medical College, Center for Neuroscience and Neuropharmacology, Albany, NY, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Feustel
authors.affiliation: CNY Fertility Center, Latham, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Grossman
authors.affiliation: CNY Fertility Center, Latham, NY, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Ditkoff
authors.affiliation: Albany Medical Center, Division of Urology, Albany, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: McCullough
mesh_terms: D000077384:Anastrozole; D002996:Clomiphene / Q000627:therapeutic use*; D004311:Double-Blind Method; D005303:Fertility Agents, Male / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy*; D007248:Infertility, Male / Q000188:drug therapy*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D011446:Prospective Studies; D013739:Testosterone / Q000097:blood* / Q000172:deficiency; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D005303:Fertility Agents, Male; D006728:Hormones; D009570:Nitriles; D014230:Triazoles; D002996:Clomiphene; D000077384:Anastrozole; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Anastozole; Clomiphene Citrate; Hypogonadism; Infertility; Testosterone