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Cited by 168Reproductive Health and ContraceptionDiabetes, Cardiovascular Risks, and LipoproteinsOvarian function and disorders

Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus

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Lopez, Laureen M, Grimes, David A, Schulz, Kenneth F·2014·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd006133.pub5PMC PMC6846331
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Abstract

BACKGROUND: Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised primarily with contraceptives containing estrogen. OBJECTIVES: To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight. SEARCH METHODS: In April 2014, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. The initial search also included EMBASE. SELECTION CRITERIA: All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin measures. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated. MAIN RESULTS: We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome.Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36).Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38).Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73).Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly. AUTHORS' CONCLUSIONS: Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods.We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).

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  • COCP does not have any major effects on carbohydrate metabolism in healthy women.

    “COCP does not have any major effects on carbohydrate metabolism in healthy women, whereas the effect on lipid metabolism depends on the level of estrogen and type of progestin, with potential negative effects (78, 79, 80, 81).”

    From Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis (2024) · cites this paper as [80]

  • The effect of COCP on lipid metabolism depends on the level of estrogen and type of progestin, with potential negative effects.

    “COCP does not have any major effects on carbohydrate metabolism in healthy women, whereas the effect on lipid metabolism depends on the level of estrogen and type of progestin, with potential negative effects (78, 79, 80, 81).”

    From Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis (2024) · cites this paper as [80]

    The Discussion supports the sentence’s separate carbohydrate-metabolism statement, but not the attributed claim about lipids. The Methods list glucose and insulin outcomes; searches for lipid metabolism, lipid profiles, cholesterol, and triglycerides found no passage assessing whether lipid effects depend on estrogen level or progestin type or describing potential negative lipid effects. (LLM, conf=0.76)

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Cites

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4 of the 119 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Michal F. Safety Requirements for Contraceptive Steroids. New York: Cambridge University Press, 1989. [Google Scholar]
  2. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Journal of the American Medical Association 1995;273:408‐12. [DOI] [PubMed] [Google Scholar]
  3. Wallach M, Grimes DA. Modern Oral Contraception. Updates from the Contraception Report. Totowa (NJ): Emron, 2000. [Google Scholar]

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Authors
Lopez, L. M., Grimes, D. A., & Schulz, K. F.
Affiliations
  • Family Health International 360 (US)
  • University of North Carolina at Chapel Hill (US)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2014-04-30
Volume
2019
Issue
11
Pages
CD006133-CD006133
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd006133.pub5
PMC
PMC6846331
OpenAlex
W1882753033
Cited by
166
References
119
Citations by year
2026: 4 · 2025: 4 · 2024: 7 · 2023: 26 · 2022: 11 · 2021: 10 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 14 · 2015: 10 · 2014: 4 · 2013: 7 · 2012: 11
FWCI
2.04
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Keywords
hormonal contraception, carbohydrate metabolism, glucose tolerance, insulin resistance, combined oral contraceptives, progestin-only pills, injectable contraceptives, contraceptive implants, vaginal ring, desogestrel, levonorgestrel, fasting blood glucose, type 2 diabetes risk, cardiovascular risk, overweight women, randomized controlled trials, meta-analysis of trials
MeSH terms
Contraceptives, Oral, Combined, Contraceptives, Oral, Hormonal, Dietary Carbohydrates, Fasting, Female, Glucose, Humans, Insulin, Insulin Resistance, Progestins, Randomized Controlled Trials as Topic, Overweight

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