title: Predicting biochemical response to clomiphene citrate in men with hypogonadism.
abstract: BACKGROUND
  Clomiphene citrate (CC) is as an effective treatment for men with hypogonadism (HG). Identifying the ideal candidate for this strategy has to date largely relied upon a patient's interest in preservation of testicular volume and spermatogenesis.
  
  
  OBJECTIVE
  This analysis was undertaken to define if predictors existed of robust elevation in serum testosterone (T) levels in response to CC.
  
  
  METHODS
  Seventy-six men with a diagnosis of HG (two separate early morning total T levels <300 ng/dL) opting for CC therapy constituted the study population. Demographic, comorbidity data, and physical and laboratory characteristics were recorded. Laboratory tests were conducted 4 weeks after commencement and every 6 months thereafter. Multivariable analysis was conducted to define if predictors of biochemical response could be identified. Parameters included in the model were patient age, mean testicular volume, varicocele presence, and baseline total T, free T, and luteinizing hormone (LH) levels.
  
  
  METHODS
  Successful biochemical response to CC, defined as an increase of ≥200 ng/dL in total T level at ≥6 months after commencing CC, was the main outcome measure.
  
  
  RESULTS
  Mean age was 46 ± 22 years. Mean pretreatment testicular volume was 16 ± 8 mL. Mean baseline T and LH levels were 179 ± 72 ng/dL and 7.2 ± 5.6 IU/mL, respectively. Mean total T on CC was 467 ± 190 ng/dL. Forty-seven patients (62%) met the responder definition, with a mean increase in total T levels of 302 ± 76 (204-464) ng/dL. In CC responders, the mean LH rise was 5.6 ± 3.1 IU/mL. On multivariable analysis, factors predictive of CC response included: mean testicular volume (adjusted [adj.] r = 0.32, P < 0.01), mean testicular volume ≥14 mL (hazard ratio [HR] 2.2, P < 0.01), LH level (adj. r = 0.48, P < 0.001), and LH level ≤6 IU/mL (HR 3.5, P < 0.001).
  
  
  CONCLUSIONS
  These data indicate that two thirds of men with HG meet a robust responder definition and that pretreatment testicular volume and LH levels (in continuous and dichotomized fashions) are predictors of response.
authors.affiliation: Sexual Medicine Clinic, Memorial Sloan-Kettering Cancer Center, New York City, NY, USA.
authors.forename: Clarisse R
authors.initials: CR
authors.lastname: Mazzola
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Katz
authors.forename: Nina
authors.initials: N
authors.lastname: Loghmanieh
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Nelson
authors.forename: John P
authors.initials: JP
authors.lastname: Mulhall
mesh_terms: D000328:Adult; D000368:Aged; D002996:Clomiphene / Q000627:therapeutic use*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D002996:Clomiphene
keywords: Clomiphene Citrate; Hypogonadism; Infertility; LH; Secondary Hypogonadism; Testicular Atrophy; Testosterone; Testosterone Replacement Therapy