I want to know
(a) What is role of insulin in androgen synthesis.
(b) Does hyperinsulinemia stimulate over-expression of androgen. If yes, How?
(c) Does PCOS change the interaction dynamics between insulin and androgens?
Dear Shayaq Ul Abeer,
Maybe the following papers will help you:
Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010;122(1-3):42-52. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846536/pdf/nihms3752.pdf
Asagami T, Holmes TH, Reaven G. Differential effects of insulin sensitivity on androgens in obese women with polycystic ovary syndrome or normal ovulation. Metabolism. 2008;57(10):1355-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2573867/pdf/nihms71936.pdf
Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002;26(7):883-96. https://www.nature.com/ijo/journal/v26/n7/pdf/0801994a.pdf
Rae M, Grace C, Hogg K, Wilson LM, McHaffie SL, Ramaswamy S, MacCallum J, Connolly F, McNeilly AS, Duncan C. The pancreas is altered by in utero androgen exposure: implications for clinical conditions such as polycystic ovary syndrome (PCOS). PLoS One. 2013;8(2):e56263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574134/pdf/pone.0056263.pdf
Parra A, Barrón J, Mota-González M, Ibarra V, Espinosa de los Monteros A. Serum androgen changes during meal-induced hyperinsulinemia and after acute sequential blockade and hyperstimulation of insulin release in women with polycystic ovary syndrome. Arch Med Res. 1995;26 Spec No:S209-17. https://www.ncbi.nlm.nih.gov/pubmed/8845652
Yildizhan B, Anik Ilhan G, Pekin T. The impact of insulin resistance on clinical, hormonal and metabolic parameters in lean women with polycystic ovary syndrome. J Obstet Gynaecol. 2016;36(7):893-896. http://www.tandfonline.com/doi/abs/10.3109/01443615.2016.1168376
Best wishes from Germany,
Martin
Dear Shayaq Ul Abeer,
Trikudanathan S. Polycystic ovarian syndrome. Med Clin North Am. 2015
Jan;99(1):221-35. doi: 10.1016/j.mcna.2014.09.003. Epub 2014 Nov 22. Review.
PubMed PMID: 25456652. Sincerely
Through the direct action of insulin in inhibiting Sex hormone binding globulin (SHBG). As SHBG decreases, the free testosterone in circulation secreted from ovary and adrenal glands increases, leading to symptoms of PCOS.
This link of article is useful
http://care.diabetesjournals.org/content/28/7/1636
Regards
Many colleagues have shared important papers and information to answer your questions. I'd like to complement it by saying that hyperinsulinemia can create a PCOS-like feature without hyperandrogenism. We have showed that recently by using a hyperinsulinemic rodent model that does not have a functioning hypothalamus-pituitary-gonads axis. Details can be found on the attached document. If you're interested in knowing more or have questions or suggestions, please drop me a message as I'm always happy to talk about science!
The primary defect, central to PCOS is “insulin resistance” which leads to various changes in metabolic pathways especially in the liver. So specifically coming to your question, I guess following processes lead to hyper-androgenemia in insulin resistance:
1- Reduced production of SHBG (Sex hormone binding globulins), so whatever testosterone, it becomes free and that is why few studies have shown higher free androgen index, which is calculated by formula available as :
https://www.nebido.com/en/hcp/research/testosterone-tools/free-calculator.php.
There are also other formulas.
2- The second issues is the higher production of androgens by the ovaries. At ovarian level the insulin resistance leads defective actions of FSH, IGFs which ultimately leads to higher androgens.
However, the base line defects also include altered GnRH secretion which kind of raises more LH in comparison to FSH as depicted in schematic below:
https://www.dialdish.com/wp-content/uploads/2018/02/polycystic-ovary-syndrome-3-638-638x445.jpg.
3. Adrenal glands are also affected (albeit not well-evidenced) to generate more DHEAS
So these multiple factors probably leads to raised androgens levels.
However, I am also not clear other factors including genetics and epigenetics in terms of their effects towards appearance of PCOS and PCOS phenotypes vary and sometimes there is no insulin resistance with an apparent PCOS like phenotype. For these queries I have raised a separate question, and if u could or other address that, I will be grateful.
I hope it would help.
Regards
Insulin plays a multifaceted role in regulating androgen production in PCOS by directly stimulating ovarian androgen synthesis, reducing SHBG levels, disrupting follicle development, and influencing gonadotropin secretion. Managing insulin resistance through lifestyle modifications, medications such as insulin-sensitizing agents (e.g., metformin), and dietary interventions is an important aspect of PCOS treatment aimed at reducing hyperinsulinemia and mitigating androgen excess.
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