Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome

Nicholas A. Cataldo, Huiman X. Barnhart, Richard S. Legro, Evan R. Myers, William D. Schlaff, Bruce R. Carr, Michael P. Diamond, Sandra A. Carson, Michael P. Steinkampf, Christos Coutifaris, Peter G. McGovern, Gabriella Gosman, John E. Nestler, Linda C. Giudice

Research output: Contribution to journalArticle

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Abstract

Context: 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. Design: 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. Setting: Study volunteers at multiple academic medical centers were included. Participants: 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. Interventions: 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. Main Outcome Measures: 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. Conclusion: Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.

Original languageEnglish (US)
Pages (from-to)3124-3127
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number8
DOIs
StatePublished - Aug 2008

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Clomiphene
Polycystic Ovary Syndrome
Metformin
Ovulation
National Institute of Child Health and Human Development (U.S.)
Reproductive Medicine
Pregnancy
Ovulation Induction
Controlled Clinical Trials
Serum
Multicenter Studies
Medicine
Progesterone
Fertility
Testosterone
Volunteers
Placebos
Outcome Assessment (Health Care)
Health

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome. / Cataldo, Nicholas A.; Barnhart, Huiman X.; Legro, Richard S.; Myers, Evan R.; Schlaff, William D.; Carr, Bruce R.; Diamond, Michael P.; Carson, Sandra A.; Steinkampf, Michael P.; Coutifaris, Christos; McGovern, Peter G.; Gosman, Gabriella; Nestler, John E.; Giudice, Linda C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 8, 08.2008, p. 3124-3127.

Research output: Contribution to journalArticle

Cataldo, NA, Barnhart, HX, Legro, RS, Myers, ER, Schlaff, WD, Carr, BR, Diamond, MP, Carson, SA, Steinkampf, MP, Coutifaris, C, McGovern, PG, Gosman, G, Nestler, JE & Giudice, LC 2008, 'Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome', Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 8, pp. 3124-3127. https://doi.org/10.1210/jc.2008-0287
Cataldo, Nicholas A. ; Barnhart, Huiman X. ; Legro, Richard S. ; Myers, Evan R. ; Schlaff, William D. ; Carr, Bruce R. ; Diamond, Michael P. ; Carson, Sandra A. ; Steinkampf, Michael P. ; Coutifaris, Christos ; McGovern, Peter G. ; Gosman, Gabriella ; Nestler, John E. ; Giudice, Linda C. / Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2008 ; Vol. 93, No. 8. pp. 3124-3127.
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T1 - Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome

AU - Cataldo, Nicholas A.

AU - Barnhart, Huiman X.

AU - Legro, Richard S.

AU - Myers, Evan R.

AU - Schlaff, William D.

AU - Carr, Bruce R.

AU - Diamond, Michael P.

AU - Carson, Sandra A.

AU - Steinkampf, Michael P.

AU - Coutifaris, Christos

AU - McGovern, Peter G.

AU - Gosman, Gabriella

AU - Nestler, John E.

AU - Giudice, Linda C.

PY - 2008/8

Y1 - 2008/8

N2 - Context: 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. Design: 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. Setting: Study volunteers at multiple academic medical centers were included. Participants: 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. Interventions: 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. Main Outcome Measures: 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. Conclusion: Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.

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