Metformin, a therapy generally used in adults with type 2 diabetes, was linked to short-term improvements in the cardiometabolic health of teenagers with polycystic ovary syndrome (PCOS), a small evidence review found.
In addition, metformin was associated with similar, short-term improvements in women with PCOS, either as monotherapy or dual therapy with estrogen-progestin oral contraception, reported Errol Fields, MD and Maria E. Trent, MD, both of Johns Hopkins University in Baltimore.
Writing in JAMA Pediatrics, Fields and Trent sought to examine the studies published on the cardiometabolic effects of treatment of PCOS in adolescents since the Endocrine Society published their clinical practice guidelines in 2013. Oral contraception has been described as a first-line treatment for adolescents with PCOS, but this therapy has been associated with an increase in metabolic dysfunction and risk for cardiovascular disease.
Of the 16 total studies the authors found, only four specifically examined cardiometabolic disturbances in adolescents with PCOS -- which Fields characterized as surprising.
"Perhaps most surprising was the lack of adolescent specific studies identified through our review," he wrote in an email to MedPage Today. "It's a relatively common condition diagnosed and treated in adolescent medicine so we expected to see more studies with adolescent participants."
Metformin is traditionally used for treating type 2 diabetes or impaired glucose tolerance in adults where lifestyle modification has failed or for women who are unable to tolerate oral contraception. However, it has not been recommended for adolescents due to "limited data."
There were two randomized trials examining metformin use in an exclusively adolescent population. One study examined metformin monotherapy as compared with oral contraception monotherapy and found a nonsignificant trend toward improved effects in the metformin group, while the oral contraception group reported a decrease in free testosterone and sex hormone-binding globulin levels, as well as an increase in menstrual cycles. Both groups reported significant decreases in BMI.
Another study examined metformin versus placebo in adolescents with PCOS found that metformin was linked to a significant decrease in sleep disturbances, as well as weight and BMI, compared with controls.
In addition, a retrospective medical record review of adolescent girls found similar results. Metformin therapy was associated with improved lipid panels compared to oral contraception therapy, even after controlling for baseline BMI and BMI changes.
"While not surprising, it was interesting to see that the majority of the studies focused on metformin as a therapeutic strategy either as monotherapy or dual therapy despite not being indicated as a first line therapy in the endocrine society guidelines," said Fields.
Metformin therapy was also beneficial in adults with PCOS. A cross-over trial (with participants ages 18-36) found that, when comparing oral contraceptives with cyproterone acetate to metformin, those in the oral contraceptive group gained a significantly greater amount of weight following the treatment compared with the metformin group.
In the two studies evaluating treatment with metformin in conjunction with oral contraception or compared with dual therapy in adults, the metformin groups were associated with significant improvements in cardiometabolic outcomes. An additional trial comparing oral contraception and metformin dual therapy with contraception alone found reductions in abdominal fat in both groups, but no significant differences in BMI among the dual therapy group. However, the review authors noted the sample size (n=42) may have been too small to detect changes.
The remaining study with adolescents as participants examined a lifestyle-based obesity intervention and found a significant decrease in intima media thickness (which can be an early indicator of cardiovascular disease), as well as improvements in waist circumference and lipid profile, as well as significant decreases in testosterone and sex hormone-binding globulin levels.
"While not evidence of causation, this association supports the hypothesis that insulin resistance/hyperinsulinism is a mediating factor between obesity and androgen excess/ovarian dysfunction in PCOS and may be a therapeutic target for improving metabolic and androgen/ovarian symptoms," the authors wrote.
Limitations to the studies included in the review include their small sample size and relatively short-term findings, as well as the fact that the majority were focused on adults.
Fields concludes that longer-term studies are needed to assess whether metformin should be added to the treatment regimen for adolescents with PCOS.
"In the short term, there appears to be some benefit to using metformin in combination with estrogen-progestin contraceptives as dual therapy in PCOS patients without type 2 diabetes or impaired glucose tolerance," he said. "However, there continues to be several unanswered questions about the utility of dual therapy such as whether short term improvements in cardiometabolic outcomes have any impact on long term mortality/morbidity in these patients and if so at what age would it be necessary to start adding metformin to a treatment regimen to achieve these long term effects."
Fields disclosed no conflicts of interest.
Trent is a member of the Trojan Sexual Health Advisory Council, Church & Dwight, and is supported by a Hologic unrestricted research grant.
Aucun commentaire:
Enregistrer un commentaire