title: Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome.
abstract: BACKGROUND
  When used for ovulation induction, higher doses of clomiphene may lead to antiestrogenic side effects that reduce fecundity. It has been suggested that metformin in combination with clomiphene can restore ovulation to some clomiphene-resistant anovulators with polycystic ovary syndrome (PCOS).
  
  
  OBJECTIVE
  Our objective was to determine if cotreatment with extended-release metformin (metformin XR) can lower the threshold dose of clomiphene needed to induce ovulation in women with PCOS.
  
  
  METHODS
  A secondary analysis of data from the National Institute of Child Health and Human Development Cooperative Multicenter Reproductive Medicine Network prospective, double-blind, placebo-controlled multicenter clinical trial, Pregnancy in Polycystic Ovary Syndrome, was performed.
  
  
  METHODS
  Study volunteers at multiple academic medical centers were included.
  
  
  METHODS
  Women with PCOS and elevated serum testosterone who were randomized to clomiphene alone or with metformin (n = 209 in each group) were included in the study.
  
  
  METHODS
  Clomiphene citrate, 50 mg daily for 5 d, was increased to 100 and 150 mg in subsequent cycles if ovulation was not achieved; half also received metformin XR, 1000 mg twice daily. Treatment was for up to 30 wk or six cycles, or until first pregnancy.
  
  
  METHODS
  Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1-2 wk.
  
  
  RESULTS
  The overall prevalence of at least one ovulation after clomiphene was 75 and 83% (P = 0.04) for the clomiphene-only and clomiphene plus metformin groups, respectively. Using available data from 314 ovulators, the frequency distribution of the lowest clomiphene dose (50, 100, or 150 mg daily) resulting in ovulation was indistinguishable between the two treatment groups.
  
  
  CONCLUSIONS
  Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.
authors.affiliation: Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Cataldo
authors.forename: Huiman X
authors.initials: HX
authors.lastname: Barnhart
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Evan R
authors.initials: ER
authors.lastname: Myers
authors.forename: William D
authors.initials: WD
authors.lastname: Schlaff
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Carr
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Carson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Steinkampf
authors.forename: Christos
authors.initials: C
authors.lastname: Coutifaris
authors.forename: Peter G
authors.initials: PG
authors.lastname: McGovern
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gosman
authors.forename: John E
authors.initials: JE
authors.lastname: Nestler
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D006801:Humans; D008687:Metformin / Q000008:administration & dosage*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
chemical_list: D003692:Delayed-Action Preparations; D005300:Fertility Agents, Female; D002996:Clomiphene; D008687:Metformin