Obese women’s offspring have double the risk of hypospadius, and women having babies after 40 have 4x the risk of hypospadius.<p>Metformin is a drug that men are probably 100x more likely to be on at 45 vs 25. Therefore men on metformin are far more likely to be reproducing with older (and likely obese) women.<p>I’m not saying this explains all the correlation, I’m just saying if the study doesn’t really make a good effort at addressing these confounders, its not worth reading.
Whatever your opinion on metformin this study is not really providing strong enough evidence to take seriously. No one should give it any attention, except the researchers who will try and do a better one next time and hopefully can prove/disprove this important hypothesis.<p>The authors have done a lot of tests here. If you do enough tests, even on null data, you eventually get false positive results. Nevermind the effects of confounding which are difficult to control for effectively in a non-random study.<p>The smallest p-value I could find was P = 0.012. Which is for "elevated birth defect fre-
quencies among metformin-exposed offspring". This comes from a table with 6 rows of models with different OR values. Presumably they did have p-values testing if those ORs were statistically different from OR == 1. Which means one should adjust p-values by dividing the significance threshold by 6. So, 0.05/6 = 0.0083 which is smaller than 0.012. So I would be very hesitant to say that the evidence points to metformin <i>really</i> causing this. At least based on this study.
I don't get why this is called rare in the article. It's not called that in the actual study, so the article seems to do some editorializing:<p><a href="https://www.acpjournals.org/doi/10.7326/M21-4389" rel="nofollow">https://www.acpjournals.org/doi/10.7326/M21-4389</a><p>Looks like of the kids taken from dads taking metformin, .9% had a genital defect, which seems pretty high to me (defect in control is 0.24%). Granted, not as high as Thalidomide, but still, 9 in 1000 are not great odds.
Metformin is also sometimes used to induce ovulation in non-obese women of childbearing age with polycystic ovarian syndrome.[0] Luckily, this study seems to only show an effect if taken within the 90 day window before conception, so it seems to be doing something to the sperm, and not causing genetic changes. Also, of course, we'd want to see corroborating studies.<p>[0] <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200666/" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200666/</a>
It’s sad seeing the crazy downstream multigenerational damage that massive sugar consumption is causing as obesity rates reach 50%.<p>Good luck future humanity.
Metformin is the first resort in diabetes treatment. If it proves to truly increase birth defects by 40% that may have to change.<p>It was my doctor's first resort for me, but the side effects were too severe and I stopped it. He vaguely mentioned that it would help if I lost weight, but made no mention of what actually resolved my diabetes, a low carb diet. I hope that becomes the first resort. Apparently around here it's not even in the standard toolkit.
> In the United States, prescriptions to 18- to 49-year-olds with type 2 diabetes grew from fewer than 2200 in 2000 to 768,000 in 2015.<p>What the hell… that has to be a mistake? What is going on? Can poor lifestyle really cause this massive increase in young people with diabetes??
It’s so interesting that type 2 diabetes is curable with diet.<p>Type 1 is incurable.<p>My point is that the psychology of eating is so strong that people would rather take a drug that pass on birth defects to the future than change eating habits.<p>And I’m a person coming from struggling with just those habits. I think if someone could come up with a treatment to adjust mindsets - it would change healthcare forever and end the need for drugs like Metaform.
I only knew Metformin by name from HNers using it as an anti-aging wonder drug over the years: <a href="https://hn.algolia.com/?dateRange=all&page=0&prefix=false&query=Metformin&sort=byPopularity&type=comment" rel="nofollow">https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...</a>
Metformin is also pretty bad when comes to impact to testosterone levels, at least in most men.
The exact mechanism that this happens is that it saps the cholesterol from your blood. This cholesterol would otherwise be used for T production by the testes.
"The researchers analyzed records from more than 1.1 million babies born in Denmark between 1997 and 2016, using the country’s comprehensive medical registries to connect data on births, paternal metformin prescriptions, and birth defects."<p>Did they look for any defect correlated with any drug? Because if they did, random chance alone would find something.<p>Anyone read the actual study?
This doesn't change that Metformin is an extremely useful drug. Even people without the official indication take it because it reduces propensity for weight gain and cancer.<p>Maybe don't take it before trying to get pregnant. Also maybe this needs to get confirmed in larger studies and in other countries.
> "...because tens of millions of people worldwide take metformin, chiefly for type 2 diabetes."<p>In nearly all cases, T2 is preventable. That is, unlike T1, there are things an individual can do to not reach T2.
I'm 26 and have been on Metformin for almost a decade at this point and will probably be on it until I die. Thankfully though, children are not in my future.
My hypothesis is that a functional zinc deficiency is the cause of most cases of diabetes, and by taking metformin, it will at least, not correct a zinc deficiency, and probably make it worse.<p>To begin I would like to share that I was born with an undecended testicle (cryptorchidism) that had to be removed surgically when I was 3. My brother was born with hypospadia. I have been studying the genetics and environmental issues around these for the last 15 years.<p>I carry several high risk genes for diabetes but probably the most relevant is that I carry the homozygous risk alleles for rs2466293 in SLC30A8 which is a zinc transporters gene. So I absorb zinc more slowly than most people.<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428214/" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428214/</a><p>"Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents."<p>I had my serum zinc tested and it was low. So now I need to take 240mg of Zinc Sulphate and eat a lot of oysters to keep my zinc levels up.<p>I was diagnosed with Lupus and now I no longer present constant symptoms.<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544280/" rel="nofollow">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544280/</a><p>"Ikaros family zinc finger 1(IKZF1) encodes a lymphoid-restricted zinc finger transcription factor named Ikaros that regulates lymphocyte differentiation and proliferation as well as self-tolerance. Increasing evidence indicates that IKZF1 could contribute to the pathogenesis of autoimmune diseases."<p>So also understand that my mother had diabetes, an immune disorder, and a mood disorder, all of them linked to zinc deficiency.<p>So, in studies zinc deficiency has been linked to diabetes:<p><a href="https://www.mdpi.com/260782" rel="nofollow">https://www.mdpi.com/260782</a><p>"Zinc deficiency is a risk factor for obesity and diabetes."<p>And genital abnormalities: (This is just one study, but there are hundreds like it.)<p><a href="https://www.karger.com/Article/Fulltext/441988" rel="nofollow">https://www.karger.com/Article/Fulltext/441988</a><p>"WT1 is a transcriptional regulator with various functions including signalling in both the embryonic kidneys and gonads. Mutations in this zinc finger transcription factor are associated with Denys-Drash or Frasier syndromes, which result in a broad range of malformations including hypospadias."<p>So I do not think the problem is metformin. I think the problem is doctors not providing patients with diabetes a full nutritional workup and ignoring the role of nutrition in human health.