PCOS and Autophagy in the Ovary

Autophagy is a popular term these days in the fasting world, but many aren’t aware that it’s also crucial for ovarian function. (1). Autophagy occurs when cells self-digest parts to get rid of unwanted material. So, how does this apply to the ovary? 

First its important to know that follicles in the ovary include the oocyte (egg) surrounded by powerful cells that make most of the estrogen, progesterone and testosterone in our bodies. Granulosa cells of the follicle make primarily estradiol, and the theca cells make androgens (like testosterone). At ovulation, the egg is ejected and the follicle turns into the corpus luteum a temporary endocrine “mini-organ”. This has a lifespan of around 14 days. When the follicle becomes the corpus luteum, the granulosa cells switch to make primarily progesterone, though they still make estradiol. The theca cells continue to produce androgens, and then also produce progesterone. 
Once 14 days have passed without pregnancy, the follicle breaks down. The uterine lining is shed, and a new cycle begins. Not surprisingly, with all of these rapid cell changes – it turns out that autophagy is crucial in the maturation, development and breakdown of follicles. 

Additionally, it’s been found that autophagy also affects the survival of the granulosa cells. Changes to natural autophagy have been found in PCOS ovaries, affecting the development of oocytes and the survival of granulosa cells. This inhibits meiosis of oocytes and granulosa cells, which in turn hinders egg maturation(2,3). 

Primarily, this impact on autophagy in PCOS seems to be caused by increased levels of inflammatory cytokines such as IGF-1. Like many molecules in the ovary IGF1 is needed in a healthy balance  – too much or too little can both be a problem. IGF-1 is increased by many factors, including insulin resistance, inflammation, high androgens, and even by consuming milk/dairy protein (4).

This is important because ovarian function drives hormone balance – and goes far beyond fertility. Healthy levels of estrogen, progesterone and testosterone are key to female health on every level including the brain, immune system, skin, hair,  bone health, and much more. 

So, how can you regulate the process of ovarian autophagy, as well as promote healthy autophagy in the whole body?
For women with significant insulin resistance,  emphasize the following: 

– Balance your meals with plenty of protein, healthy fats, vegetables, and portion-controlled amounts of low-insulin-demand carbs. (This should be put into practice by all women, but those without insulin resistance often need more carbs than those with it.) 

– Exercise, especially strength training the lower body, as this invokes Glut-4 receptors.

– Intermittent fasting: at least 12 hours per day without eating. Depending on physiology, stress, and cortisol, other and more challenging fasting windows can be included.

– Supplements such as inositol, NAC, and berberine are good support for insulin resistance. 

For women both with and without insulin resistance:

– Get proper sleep and rest! Circadian rhythm is key for autophagy. 

– Manage inflammation: find your physical inflammatory triggers, such as food sensitivities, toxins, and infections.

– Manage stress and adrenal health. Cortisol dysregulation impacts Igf1(5).

– Manage excess androgens with anti-androgenic herbs or progesterone (please ask your naturopathic doctor as this part can get complicated).
For more information on this, please read my book, 8 Steps to Reverse Your PCOS, which is available on Amazon!
1) 1. Tao T, Xu H. Autophagy and Obesity-Related Reproductive Dysfunction. Adv Exp Med Biol. 2020;1207:463-466. doi:10.1007/978-981-15-4272-5_33
2) 1. Roche J, Ramé C, Reverchon M, et al. Apelin (APLN) and Apelin Receptor (APLNR) in Human Ovary: Expression, Signaling, and Regulation of Steroidogenesis in Primary Human Luteinized Granulosa Cells. Biol Reprod. 2016;95(5). doi:10.1095/biolreprod.116.141754

3)Li D, You Y, Bi F-F, et al. Autophagy is activated in the ovarian tissue of polycystic ovary syndrome. Reproduction. 2018;155(1):85-92. doi:10.1530/REP-17-0499

4) 1. Li X, Qi J, Zhu Q, et al. The role of androgen in autophagy of granulosa cells from PCOS. Gynecol Endocrinol. 2019;35(8):669-672. doi:10.1080/09513590.2018.1540567


5)1. Nassib S, Moalla W, Hammoudi-Nassib S, et al. The IGF-1/cortisol ratio as a useful marker for monitoring training in young boxers. Biol Sport. 2016;33(1):15-22. doi:10.5604/20831862.1180172