In the Journals

Hyperandrogenism may alter gut microbiome in PCOS

Thackrya Varykina
Varykina G. Thackray

White women diagnosed with polycystic ovary syndrome have a reduction in overall species richness in the gut microbiome and changes in microbial composition vs. women without PCOS, according to findings reported in The Journal of Clinical Endocrinology & Metabolism.

“Our findings suggest that androgens may be an important factor in shaping the gut microbiome, and that changes in the gut microbiome may influence the development and pathology of PCOS,” Pedro J. Torres, MS, a doctoral student with the department of biology at San Diego State University, and colleagues wrote. “If hyperandrogenism drives the microbial composition of the gut, it would be interesting to determine if treatment of PCOS with androgen antagonists or oral contraceptives results in recovery of the gut microbiome and improvement of the PCOS metabolic phenotype.”

Torres and colleagues analyzed data from 163 premenopausal women recruited at Poznan University of Medical Sciences in Poland, including 73 diagnosed with PCOS, 42 with polycystic ovarian morphology and 48 healthy controls. During a morning study visit, participants provided fasting blood samples and fecal samples and underwent a 2-hour oral glucose tolerance test and transvaginal ultrasound. Researchers measured serum testosterone, luteinizing hormone, follicle-stimulating hormone and insulin levels, as well as fecal microbial diversity using 16S rRNA gene sequencing.

Of the 73 women with PCOS, 21 met all three Rotterdam criteria (hyperandrogenism, oligomenorrhea and polycystic ovarian morphology), 39 had hyperandrogenism and polycystic ovarian morphology, two had hyperandrogenism and oligomenorrhea, and 11 had oligomenorrhea and polycystic ovarian morphology.

Researchers observed a reduced gut microbiome alpha diversity in women with PCOS when compared with healthy women as measured by abundance (P = .04) as well as reduced phylogenetic diversity (P = .02).

“We also observed an intermediate phenotype for women with [polycystic ovarian morphology] with regards to gut microbiome alpha diversity, suggesting that further studies are warranted to determine whether the gut microbiome of women with [polycystic ovarian morphology] is significantly altered compared with healthy women,” the researchers wrote.

Additionally, the Shannon diversity index, which accounts for both microbial abundance and evenness of the sequence variants, was lower in women with PCOS vs. healthy controls (P = .01). There were no between-group differences for the evenness of the gut microbiome, according to researchers.

In regression analyses, researchers found that hyperandrogenism, increased total testosterone and hirsutism were negatively correlated with alpha diversity, whereas PERMANOVA analysis showed that hyperandrogenism was also correlated with decreased beta diversity.

Random Forest machine-learning analyses also identified eight bacteria genera that discriminated between healthy women and women with PCOS.

The researchers noted that neither BMI nor homeostatic model assessment of insulin resistance correlated with changes in alpha or beta diversity of the gut microbiome, although other studies have reported such a link. One possible explanation, they added, was that the average BMI of the women was 24.32 kg/m².

“Why many women with PCOS have metabolic dysregulation (eg, weight gain, insulin resistance) that results in an increased risk of developing type 2 diabetes is not well understood, although previous studies have shown that hyperandrogenism correlates with metabolic dysregulation in women with PCOS,” resesarcher Varykina G. Thackray, PhD, associate professor of reproductive medicine at UC San Diego School of Medicine, told Endocrine Today. “The demonstration that hyperandrogenism is correlated with changes in the gut microbiome in women with PCOS suggests that elevated testosterone may influence the composition of the gut microbiome, which potentially results in metabolic changes. This study further suggests that manipulation of the gut microbiome may be a potential treatment for women with PCOS.”

Thackray said that further clinical studies and animal models can help researchers better understand how slightly higher levels of testosterone can influence the gut microbiome and metabolism in women.

“Future studies will also be needed to determine whether specific gut bacterial species play a role in the development and pathology of PCOS and whether specific pre- or probiotics could be a treatment option for women with PCOS,” Thackray said. – by Regina Schaffer

For more information:

Varykina G. Thackray, PhD, can be reached at University of California, San Diego, Department of Reproductive Medicine, MC:0674, 9500 Gilman Drive, La Jolla, CA 92093; email: vthackray@ucsd.edu.

Disclosures: The authors report no relevant financial disclosures.

 

Thackrya Varykina
Varykina G. Thackray

White women diagnosed with polycystic ovary syndrome have a reduction in overall species richness in the gut microbiome and changes in microbial composition vs. women without PCOS, according to findings reported in The Journal of Clinical Endocrinology & Metabolism.

“Our findings suggest that androgens may be an important factor in shaping the gut microbiome, and that changes in the gut microbiome may influence the development and pathology of PCOS,” Pedro J. Torres, MS, a doctoral student with the department of biology at San Diego State University, and colleagues wrote. “If hyperandrogenism drives the microbial composition of the gut, it would be interesting to determine if treatment of PCOS with androgen antagonists or oral contraceptives results in recovery of the gut microbiome and improvement of the PCOS metabolic phenotype.”

Torres and colleagues analyzed data from 163 premenopausal women recruited at Poznan University of Medical Sciences in Poland, including 73 diagnosed with PCOS, 42 with polycystic ovarian morphology and 48 healthy controls. During a morning study visit, participants provided fasting blood samples and fecal samples and underwent a 2-hour oral glucose tolerance test and transvaginal ultrasound. Researchers measured serum testosterone, luteinizing hormone, follicle-stimulating hormone and insulin levels, as well as fecal microbial diversity using 16S rRNA gene sequencing.

Of the 73 women with PCOS, 21 met all three Rotterdam criteria (hyperandrogenism, oligomenorrhea and polycystic ovarian morphology), 39 had hyperandrogenism and polycystic ovarian morphology, two had hyperandrogenism and oligomenorrhea, and 11 had oligomenorrhea and polycystic ovarian morphology.

Researchers observed a reduced gut microbiome alpha diversity in women with PCOS when compared with healthy women as measured by abundance (P = .04) as well as reduced phylogenetic diversity (P = .02).

“We also observed an intermediate phenotype for women with [polycystic ovarian morphology] with regards to gut microbiome alpha diversity, suggesting that further studies are warranted to determine whether the gut microbiome of women with [polycystic ovarian morphology] is significantly altered compared with healthy women,” the researchers wrote.

Additionally, the Shannon diversity index, which accounts for both microbial abundance and evenness of the sequence variants, was lower in women with PCOS vs. healthy controls (P = .01). There were no between-group differences for the evenness of the gut microbiome, according to researchers.

In regression analyses, researchers found that hyperandrogenism, increased total testosterone and hirsutism were negatively correlated with alpha diversity, whereas PERMANOVA analysis showed that hyperandrogenism was also correlated with decreased beta diversity.

Random Forest machine-learning analyses also identified eight bacteria genera that discriminated between healthy women and women with PCOS.

The researchers noted that neither BMI nor homeostatic model assessment of insulin resistance correlated with changes in alpha or beta diversity of the gut microbiome, although other studies have reported such a link. One possible explanation, they added, was that the average BMI of the women was 24.32 kg/m².

“Why many women with PCOS have metabolic dysregulation (eg, weight gain, insulin resistance) that results in an increased risk of developing type 2 diabetes is not well understood, although previous studies have shown that hyperandrogenism correlates with metabolic dysregulation in women with PCOS,” resesarcher Varykina G. Thackray, PhD, associate professor of reproductive medicine at UC San Diego School of Medicine, told Endocrine Today. “The demonstration that hyperandrogenism is correlated with changes in the gut microbiome in women with PCOS suggests that elevated testosterone may influence the composition of the gut microbiome, which potentially results in metabolic changes. This study further suggests that manipulation of the gut microbiome may be a potential treatment for women with PCOS.”

Thackray said that further clinical studies and animal models can help researchers better understand how slightly higher levels of testosterone can influence the gut microbiome and metabolism in women.

“Future studies will also be needed to determine whether specific gut bacterial species play a role in the development and pathology of PCOS and whether specific pre- or probiotics could be a treatment option for women with PCOS,” Thackray said. – by Regina Schaffer

For more information:

Varykina G. Thackray, PhD, can be reached at University of California, San Diego, Department of Reproductive Medicine, MC:0674, 9500 Gilman Drive, La Jolla, CA 92093; email: vthackray@ucsd.edu.

Disclosures: The authors report no relevant financial disclosures.

 

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