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Male Metformin Use Preconception Increases Birth Defect Risk

danieltx

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Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation.

https://www.acpjournals.org/doi/10.7326/M21-4389

Background:​

Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown.

Objective:​

To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes.

Design:​

Nationwide prospective registry-based cohort study.

Setting:​

Denmark from 1997 to 2016.

Participants:​

All liveborn singletons from mothers without histories of diabetes or essential hypertension.

Measurements:​

Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings.

Results:​

Of 1 116 779 offspring included, 3.3% had 1 or more major birth defects (reference). Insulin-exposed offspring (n = 5298) had the reference birth defect frequency (adjusted odds ratio [aOR], 0.98 [95% CI, 0.85 to 1.14]). Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92). Offspring whose fathers filled a metformin prescription in the year before (n = 1751) or after (n = 2484) sperm development had reference birth defect frequencies (aORs, 0.88 [CI, 0.59 to 1.31] and 0.92 [CI, 0.68 to 1.26], respectively), as did unexposed siblings of exposed offspring (3.2%; exposed vs. unexposed OR, 1.54 [CI, 0.94 to 2.53]). Among metformin-exposed offspring, genital birth defects, all in boys, were more common (aOR, 3.39 [CI, 1.82 to 6.30]), while the proportion of male offspring was lower (49.4% vs. 51.4%, P = 0.073).

Limitation:​

Information on underlying disease status was limited.

Conclusion:​

Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation.

Primary Funding Source:​

National Institutes of Health.[/quote
 
Is it the diabetes responsible for the birth defects? Or is the Metformin itself? Is a 3% risk of birth defect that much greater than the normal population’s risk for birth defects? The verbiage used here is quite misleading and not definitive at all. Left with more questions than answers and doesn’t really say a whole lot. And don’t forget that last line - “Further research should replicate these findings and clarify the causation.”

I’ll keep taking my Metformin.
 
So what’s the birth defect? Sperm count? Maybe I glossed over it. When my son was born he ended up in the NICU due to the wife developing gestational diabetes during the pregnancy. He was there for 3 days before his blood glucose levels normalized. He’s a health boy today without any issues.

Cage
 
So what’s the birth defect? Sperm count? Maybe I glossed over it. When my son was born he ended up in the NICU due to the wife developing gestational diabetes during the pregnancy. He was there for 3 days before his blood glucose levels normalized. He’s a health boy today without any issues.

Cage
Birth defects usually mean something physically with the child didn't form correctly. In this study they city genital defects in boys as the major one.
 
Birth defects usually mean something physically with the child didn't form correctly. In this study they city genital defects in boys as the major one.
Did it say what they were though? Like did their dicks not fully form, micro penis, missing a ball, small balls, some 90* bent penis, etc?

Cage
 

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