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How does PCOS affect menstrual health? 

According to a 2021 article on Research Progress on the Mechanism Between PCOS and Abnormal Endometrium, individuals with PCOS are at significantly increased risk of endometrial hyperplasia (and therefore endometrial cancer). 


Polycystic ovarian syndrome (PCOS) is one of the most common, most profound and most overlooked health conditions affecting individuals assigned female at birth.  It is a multi-system disorder which impacts hormonal, menstrual, reproductive/maternal, cardio-metabolic, oncological, mental/neurological, sexual and immune system health.  In this article we explore the link between PCOS and Menstrual Health. 

 

At its core, PCOS is associated with abnormal functioning of the system of hormones that connects the hypothalamus, the pituitary and the ovaries (the HPO-axis).[1] 

 

In individuals with PCOS, the activity level (pulse frequency) of one of the hormones produced in the hypothalamus, the Gonadotrophin Releasing Hormone (GnRH), is over-active.[2] 

  • An elevated level of GnRH triggers an elevated level of Luteinizing Hormone (LH) in the pituitary, LH and Follicle Stimulating Hormone (FSH) being the two hormones responsible for stimulating growth of follicles, the part of the ovary that contains eggs, and synchronize the release of eggs from the ovaries;[3] 

  • An elevated LH level leads to increased stimulation of theca cells, a type of cell within the ovary that plays an essential role in fertility;[4] 

  • The increased stimulation of these theca cells increases the rate of conversion of cholesterol, a fat-like substance that is found in all cells in the body and needed to make hormones,[5] to two androgens or sex hormones (androstenedione and testosterone);[6][7] 

  • A portion of these androgens then travel to neighboring granulosa cells, a type of cell within the ovary that is important for the production of reproductive hormones;[8] 

  • Within granulosa cells, some of these androgens are converted to estrogen, a sex hormone responsible for triggering egg release and thickening the lining of the uterus;[9] and 

 

Some of these excess androgens are not converted and therefore lead to an androgen-rich environment within the ovary[10] and elevated circulating androgens. 

 

As a result, PCOS is associated with hyperandrogenism (HA) or androgen excess (AE), elevated androgens in individuals assigned female at birth. 

 

A typical menstrual cycle relies on a complex interplay of chemicals over a cycle of around 28 days and comprised of four key phases:[11] 

  • Menses: the uterus sheds its lining if pregnancy hasn’t occurred from day 1 of the cycle for a typical period of 3-7 days; 

  • Follicular: overlapping with menses and lasting for 10-14 days, the lining of the uterus is restored and follicles in the ovaries grow to produce (usually) a single mature egg or ovum; 

  • Ovulation: at roughly day 14, an eggs is released; and 

  • Luteal: from day 15-28 the egg travels to the uterus and, if fertilized by a sperm, implants into the uterine wall. 

 

The hormonal imbalances associated with PCOS can interfere with the follicular phase, resulting in no one single dominant mature egg or ovum developing:[12][13] 

  • The hypothalamus (a region of your brain) releases gonadotrophin-releasing hormone (GnRH), a chemical messenger that is vital to puberty, sex drive and fertility;[14] 

  • In individuals with PCOS, the activity level (pulse frequency) of one of the hormones produced in the hypothalamus, the Gonadotrophin Releasing Hormone (GnRH), is over-active;[15]   

  • The GnRH triggers the pituitary gland (a gland at the base of the brain) to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH); 

  • Between day 6 and 14 of the menstrual cycle, FSH causes follicles, small sacs of fluid in your ovaries that contain a developing egg or oocyte, in one ovary to begin to mature; 

  • Between day 10 and 14, a dominant follicle emerges that out-competes the other follicles for FSH; 

  • This dominant follicle then secretes inhibin that reduces FSH production in effect “turning off” neighboring follicles;[16] 

  • This mature follicle develops into a fully mature egg, within what is now known as a Graafian follicle[17] and reaches up to 2.5 cm in diameter;[18] 

  • Instead, in individuals with PCOS, an elevated level of GnRH can result in over-production of LH,[19] so that follicle development stalls at the antral phase (2-9 mm in diameter)[20] and no dominant follicle emerges; 

  • In some individuals with PCOS these immature follicles can accumulate and remain as several small follicles often referred to as a “string of pearls”,[21] hence the naming of the condition as polycystic ovarian syndrome (PCOS).[22] 

 

The hormonal imbalances associated with PCOS can therefore interfere with the process of ovulation itself:[23][24] 

  • In a typical cycle, the Graafian follicle moves towards the surface of the ovary and, at around day 14, the mature follicle produces sufficient estradiol to trigger an LH surge which kicks off the steps towards ovulation; 

  • In an individual with PCOS none of the small immature follicles is typically capable of growing to a size that would be sufficient to trigger this LH surge.[25] 

 

As a result, PCOS is associated with amenorrhea (absent periods) and dysmenorrhea (irregular menstruation with 8 or fewer periods in a year).[26]  An estimated 85-90% of individuals with PCOS experience irregular or infrequent periods.[27]  

 

Amenorrhea and dysmenorrhea mean that the endometrium, the lining of the uterus, does not shed in a regular monthly cycle.[28]  In parallel, the ovaries continue to produce estrogen despite the failure to ovulate resulting in an estrogen rich environment.  The endometrial cells that remain in place for an extended period of time are exposed to estrogen and therefore continue to grow and thicken the endometrium. a process known as hyperplasia.[29]  Individuals with PCOS may be at 10x the risk of developing endometrial hyperplasia relative to individuals without PCOS.[30][31]  

 

Endometrial hyperplasia can cause heavy menstrual bleeding (HMB), bleeding between periods, short menstrual cycles of less than 21 days and/or bleeding from the vagina post menopause.[32][33] 

   

No explicit link has firmly been established between PCOS and premenstrual dysmorphic disorder (PMDD),[34] an extreme form of premenstrual syndrome (PMS) with significant mental and physical impairments in the week leading up to menses, the onset of a period, and then improvement in or absence of symptoms in the intervening weeks.[35]  However, individuals with PCOS have a significantly increased likelihood of having autism and/or attention deficit hyperactivity disorder or ADHD.  While only 3-9% of the population experience PMDD,[36] one study found that 46% of women with ADHD and 92% of those with autism have a diagnosis of PMDD.[37] 

 

Overall risk factors for menstrual health include:[38] 

  • Family history of menstrual irregularities; 

  • Personal history of certain gynecologic procedures including dilation and curettage (D&C) and loop electro-diathermy excision procedure (LEEP); 

  • Menopause or premature menopause (before the age of 40); 

  • Abnormal functioning of the thyroid gland, either hyperthyroidism or hypothyroidism; 

  • Pituitary tumor or damage to the pituitary glad; 

  • Abnormalities of the uterus that are either present from birth or caused due to injury and/or surgery; 

  • Use of certain medications such as antipsychotics, chemotherapy drugs, antidepressants, blood pressure medication and allergy medications; 

  • High or low BMI; 

  • Eating disorders; 

  • Strenuous exercise (can prevent ovulation); and 

  • Stress. 

 

Sources
[1] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 
[2] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 
[3] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 
[4] https://pubmed.ncbi.nlm.nih.gov/15833266/ 
[5] https://my.clevelandclinic.org/health/articles/23922-what-is-cholesterol 
[6] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 
[7] https://my.clevelandclinic.org/health/articles/22002-androgens 
[8] https://my.clevelandclinic.org/health/body/22528-granulosa-cells 
[9] https://my.clevelandclinic.org/health/body/22353-estrogen 
[10] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 
[11] https://my.clevelandclinic.org/health/articles/10132-menstrual-cycle 
[12] https://my.clevelandclinic.org/health/diseases/21698-anovulation 
[13] https://www.ncbi.nlm.nih.gov/books/NBK279054/ 
[14] https://my.clevelandclinic.org/health/body/22525-gonadotropin-releasing-hormone 
[15] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 
[16] https://www.ncbi.nlm.nih.gov/books/NBK441996/ 
[17] https://byjus.com/question-answer/what-is-a-graafian-follicle-in-the-ovary/ 
[18] https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/graafian-follicles  
[19] https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00416-4/fulltext 
[20] https://advancedfertility.com/infertility-testing/antral-follicle-counts/ 
[21] https://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics 
[22] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882969/ 
[23] https://my.clevelandclinic.org/health/diseases/21698-anovulation 
[24] https://www.ncbi.nlm.nih.gov/books/NBK279054/ 
[25] https://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics 
[26] https://www.verywellhealth.com/oligoovulation-2616419 
[27] https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.873726/full 
[28] https://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics/ 
[29] https://www.acog.org/womens-health/faqs/endometrial-hyperplasia 
[30] https://www.jogcr.com/article_708957.html 
[31] https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.788772/full 
[32] https://my.clevelandclinic.org/health/diseases/16569-atypical-endometrial-hyperplasia 
[33] https://www.acog.org/womens-health/faqs/endometrial-hyperplasia 
[34] https://ada.com/conditions/premenstrual-dysphoric-disorder-pmdd/ 
[35] https://www.additudemag.com/pmdd-autism-adhd/#footnote6 
[36] https://www.additudemag.com/pmdd-autism-adhd/#footnote6 
[37] https://www.sciencedirect.com/science/article/abs/pii/S0022395620311134?via%3Dihub 
[38] https://www.mayoclinic.org/diseases-conditions/amenorrhea/symptoms-causes/syc-20369299 

Causes - Menstrual

PCOS and Menstrual Health

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