Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome.
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.
Cataldo
Nicholas A
NA
Stanford University School of Medicine, Stanford, CA 94305, USA.
Barnhart
Huiman X
HX
Legro
Richard S
RS
Myers
Evan R
ER
Schlaff
William D
WD
Carr
Bruce R
BR
Diamond
Michael P
MP
Carson
Sandra A
SA
Steinkampf
Michael P
MP
Coutifaris
Christos
C
McGovern
Peter G
PG
Gosman
Gabriella
G
Nestler
John E
JE
Giudice
Linda C
LC
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
D003692:Delayed-Action Preparations; D005300:Fertility Agents, Female; D002996:Clomiphene; D008687:Metformin