Hypothesis: Metformin is a potential reproductive toxicant
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Hypothesis : Metformin is a potential reproductive toxicant. / Tavlo, Maja; Skakkebæk, Niels E.; Mathiesen, Elisabeth R.; Kristensen, David M.; Kjær, Kurt H.; Andersson, Anna-Maria; Lindahl-Jacobsen, Rune.
In: Frontiers in Endocrinology, Vol. 13, 1000872, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Hypothesis
T2 - Metformin is a potential reproductive toxicant
AU - Tavlo, Maja
AU - Skakkebæk, Niels E.
AU - Mathiesen, Elisabeth R.
AU - Kristensen, David M.
AU - Kjær, Kurt H.
AU - Andersson, Anna-Maria
AU - Lindahl-Jacobsen, Rune
PY - 2022
Y1 - 2022
N2 - Metformin is the first-line oral treatment for type 2 diabetes mellitus and is prescribed to more than 150 million people worldwide. Metformin's effect as a glucose-lowering drug is well documented but the precise mechanism of action is unknown. A recent finding of an association between paternal metformin treatment and increased numbers of genital birth defects in sons and a tendency towards a skewed secondary sex ratio with less male offspring prompted us to focus on other evidence of reproductive side effects of this drug. Metformin in humans is documented to reduce the circulating level of testosterone in both men and women. In experimental animal models, metformin exposure in utero induced sex-specific reproductive changes in adult rat male offspring with reduced fertility manifested as a 30% decrease in litter size and metformin exposure to fish, induced intersex documented in testicular tissue. Metformin is excreted unchanged into urine and feces and is present in wastewater and even in the effluent of wastewater treatment plants from where it spreads to rivers, lakes, and drinking water. It is documented to be present in numerous freshwater samples throughout the world - and even in drinking water. We here present the hypothesis that metformin needs to be considered a potential reproductive toxicant for humans, and probably also for wildlife. There is an urgent need for studies exploring the association between metformin exposure and reproductive outcomes in humans, experimental animals, and aquatic wildlife.
AB - Metformin is the first-line oral treatment for type 2 diabetes mellitus and is prescribed to more than 150 million people worldwide. Metformin's effect as a glucose-lowering drug is well documented but the precise mechanism of action is unknown. A recent finding of an association between paternal metformin treatment and increased numbers of genital birth defects in sons and a tendency towards a skewed secondary sex ratio with less male offspring prompted us to focus on other evidence of reproductive side effects of this drug. Metformin in humans is documented to reduce the circulating level of testosterone in both men and women. In experimental animal models, metformin exposure in utero induced sex-specific reproductive changes in adult rat male offspring with reduced fertility manifested as a 30% decrease in litter size and metformin exposure to fish, induced intersex documented in testicular tissue. Metformin is excreted unchanged into urine and feces and is present in wastewater and even in the effluent of wastewater treatment plants from where it spreads to rivers, lakes, and drinking water. It is documented to be present in numerous freshwater samples throughout the world - and even in drinking water. We here present the hypothesis that metformin needs to be considered a potential reproductive toxicant for humans, and probably also for wildlife. There is an urgent need for studies exploring the association between metformin exposure and reproductive outcomes in humans, experimental animals, and aquatic wildlife.
KW - metformin
KW - reproductive toxicant
KW - testosterone
KW - endocrine disruptor
KW - environment
KW - wildlife
KW - development
KW - ENDOCRINE DISRUPTION
KW - SEX-RATIO
KW - EXPOSURE
KW - MECHANISMS
U2 - 10.3389/fendo.2022.1000872
DO - 10.3389/fendo.2022.1000872
M3 - Journal article
C2 - 36339411
VL - 13
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 1000872
ER -
ID: 325835267