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Metformin and Sexual Function: What the Evidence Actually Shows

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At a glance

  • Drug / metformin, an oral biguanide, prescription only [1]
  • Labeled use / type 2 diabetes, adults and children 10 and older (immediate-release) [1]
  • Sexual dysfunction among label adverse reactions / not listed [1]
  • Erectile dysfunction in diabetes / 66.3% in type 2, 52.5% overall (145 studies, 88,577 men) [2]
  • Human androgen data / one 6-month study of 45 men: androgens rose, semen improved [3]

Is sexual dysfunction a listed metformin side effect?

No. The label's adverse reactions section, from a US trial of 141 metformin and 145 placebo patients, lists diarrhea 53% versus 12%, nausea and vomiting 26% versus 8%, flatulence 12% versus 6% and headache 6% versus 5%, and diarrhea led to discontinuation in 6%. Postmarketing liver injury is also listed [1]. Sexual dysfunction, low libido and erectile dysfunction do not appear in that section [1]. The label's warnings include lactic acidosis, vitamin B12 deficiency and hypoglycemia when metformin is combined with insulin or an insulin secretagogue [1].

What does diabetes itself do to sexual function?

A meta-analysis of 145 studies covering 88,577 men put erectile dysfunction prevalence in diabetes at 52.5% after adjusting for publication bias: 37.5% in type 1 and 66.3% in type 2, with 3.62 times the odds of controls (95% CI 2.53 to 5.16) [2]. In women, most studies report more sexual dysfunction in those with diabetes, but the evidence is less conclusive and appears more related to social and psychological factors than to the physiology of diabetes [4].

Does metformin change testosterone or sperm?

In one study, 45 men with metabolic syndrome and poor semen parameters took metformin for 6 months; insulin resistance and sex hormone-binding globulin fell significantly, serum androgen levels rose significantly and semen characteristics improved [3].

Laboratory work points the other way. In human and mouse testis cultures metformin reduced testosterone secretion, with a lowest effective concentration of 50 micromolar in human tissue, and pregnant mice given metformin had smaller fetal and neonatal testes and lower fetal Leydig cell testosterone content [5]. Those are culture and mouse results, not measurements from men taking tablets.

On reproduction, the label advises telling premenopausal women about the potential for an unintended pregnancy and notes that metformin may result in ovulation in some anovulatory women [1].

What about women with PCOS?

Metformin is not labeled for PCOS; the labeled indication is type 2 diabetes, so PCOS use is off-label [1]. PCOS affects 4% to 12% of women, and metformin's place in it has narrowed: early studies were encouraging, but randomized trials and meta-analyses contracted its role [6].

Weight loss and erectile function

The available erectile function data on weight loss come from a lifestyle trial, not from metformin. In a Look AHEAD substudy of overweight or obese men with type 2 diabetes, the intensive lifestyle group lost 9.9% of body weight at 1 year versus 0.6% in the control group. Erectile function scores improved more in the lifestyle group (P=0.04), but the difference was no longer statistically significant after adjusting for baseline differences (P=0.06) [9].

HealthRX.com offers metformin by prescription.

Frequently asked questions

Does metformin cause erectile dysfunction?
The label does not list erectile dysfunction among its adverse reactions [1]. Erectile dysfunction is common in diabetes itself: 66.3% of men with type 2 diabetes in a meta-analysis of 145 studies, and 3.62 times the odds of men without diabetes [2].
Does metformin lower testosterone in men?
The data point in different directions. In one 6-month study of 45 men with metabolic syndrome, serum androgen levels rose significantly with metformin and semen characteristics improved [3]. In human testis cultures and in pregnant mice, metformin reduced testosterone secretion and fetal Leydig cell testosterone content [5].
Can metformin affect male fertility?
One study of 45 men with poor semen parameters found semen characteristics improved after 6 months of metformin [3]. The animal and culture work concerns fetal testicular development rather than adult sperm production [5].
Is sexual dysfunction listed as a metformin side effect?
No. The reactions above 5% are diarrhea, nausea and vomiting, flatulence, asthenia, indigestion, abdominal discomfort and headache, and postmarketing liver injury is also listed [1]. Sexual dysfunction, low libido and erectile dysfunction are not among them [1].

References

  1. U.S. National Library of Medicine, DailyMed. Metformin hydrochloride tablets (Granules, immediate-release) prescribing information. Metformin hydrochloride tablets (Granules, immediate-release) label
  2. Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo A, et al. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabet Med. 2017;34(9):1185-1192. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies
  3. Morgante G, Tosti C, Orvieto R, Musacchio MC, Piomboni P, De Leo V. Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome. Fertil Steril. 2011;95(6):2150-2. Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome
  4. Maiorino MI, Bellastella G, Esposito K. Diabetes and sexual dysfunction: current perspectives. Diabetes Metab Syndr Obes. 2014;7:95-105. Diabetes and sexual dysfunction: current perspectives
  5. Tartarin P, Moison D, Guibert E, Dupont J, Habert R, Rouiller-Fabre V, et al. Metformin exposure affects human and mouse fetal testicular cells. Hum Reprod. 2012;27(11):3304-14. Metformin exposure affects human and mouse fetal testicular cells
  6. Lashen H. Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2010;1(3):117-28. Role of metformin in the management of polycystic ovary syndrome
  7. Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-61. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study
  8. Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012;35(4):731-7. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study
  9. Wing RR, Rosen RC, Fava JL, Bahnson J, Brancati F, Gendrano Iii IN, et al. Effects of weight loss intervention on erectile function in older men with type 2 diabetes in the Look AHEAD trial. J Sex Med. 2010;7(1 Pt 1):156-65. Effects of weight loss intervention on erectile function in older men with type 2 diabetes in the Look AHEAD trial
Evidence overview for Metformin and Sexual Function: What the Evidence Actually Shows