What is the link between PMOS and Ovulatory Dysfunction? 

According to the 2023 International Evidence-Based Guidelines for the Assessment and Management of PCOS, ovulatory dysfunction, a condition where an individual doesn’t ovulate regularly (or at all), is one of the core features of PMOS. 

PMOS is the #1 cause of ovulatory dysfunction, responsible for 70% of cases of anovulation or oligo-ovulation.[1]  Ovulatory dysfunction is absent (anovulation) or irregular (oligo-ovulation) release of any egg (ovulation) during a menstrual cycle in the reproductive years.[2]  In this article we explore the link between PMOS and Ovulatory Dysfunction.

Anovulation is defined as the failure of the ovary to release an egg during a menstrual cycle.  Oligo-ovulation is defined as an interval between periods exceeding 35 days and/or less than 9 periods in a year.[3]

A typical menstrual cycle relies on a complex interplay of chemicals over a cycle of around 28 days and comprised of four key phases:[4]

• 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 PMOS can interfere with the follicular phase, resulting in no one single dominant mature egg or ovum developing:[5][6]

• The hypothalamus (a region of your brain) releases gonadotrophin-releasing hormone (GnRH), a chemical messenger that is vital to puberty, sex drive and fertility;[7]

• In individuals with PMOS, the activity level (pulse frequency) of one of the hormones produced in the hypothalamus, the GnRH, is over-active;[8]

• 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;[9]

• This mature follicle develops into a fully mature egg, within what is now known as a Graafian follicle[10] and reaches up to 2.5 cm in diameter;[11]

• Instead, in individuals with PMOS, elevated levels of GnRH in individuals with PMOS can result in over-production of LH,[12] so that follicle development stalls at the antral phase (2-9 mm in diameter)[13] and no dominant follicle emerges;

• In some individuals with PMOS these immature follicles can accumulate and remain as several small follicles often referred to as a “string of pearls”,[14] hence the historical naming of the condition as polycystic ovarian syndrome (PCOS).[15]

The hormonal imbalances associated with PMOS can therefore interfere with the process of ovulation itself:[16][17]

• 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 PMOS none of the small immature follicles is typically capable of growing to a size that would be sufficient to trigger this LH surge.[18]

As a result, PMOS is associated with anovulation and oligo-ovulation (sporadic ovulation).[19]

Other potential causes of ovulatory dysfunction include:[20]

• Depression or stress that results in an imbalance of GnRH, LH and FSH;[21]

• Early menstrual cycles, prior to establishing the hormonal balance required for ovulation or late menstrual cycles, during peri-menopause;

• Having a very high body weight (high androgen)[22] or low body weight (LH/FSH imbalance);[23]

• Being pregnant or breastfeeding (high prolactin);

• Hyperprolactinemia, abnormally high levels of prolactin, a hormone responsible for breast tissue development and lactation;[24]

• Hypothalamic-pituitary dysfunction, a range of conditions where the hypothalamus and/or pituitary gland don’t function properly;[25]

• A pituitary gland tumor or damage to the pituitary gland (LH/FSH imbalance or high prolactin);[26]

• Other pituitary gland disorders such as Cushing’s syndrome (excessive levels of cortisol hormone),[27] acromegaly (excessive levels of growth hormone)[28] or Sheehan’s syndrome (caused by severe blood loss during childbirth);[29]

• Thyroid surgery, radiation therapy or other forms of damage to the thyroid (underactive thyroid);[30]

• Hypothyroidism or hyperthyroidism, under or over-activity of the thyroid gland respectively;

• Hashimoto’s thyroiditis, an autoimmune disease (underactive thyroid);[31]

• Type 1 or type 2 diabetes;[32]

• The use of certain medications that contain estrogens or progestins and anti-depressants;

• Damage to the kidneys, liver and/or thyroid (high prolactin); or

• Damage to the hypothalamus (low GnRH).

Sources 

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC7846416/

[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC9527465/

[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC10683967/

[4] https://my.clevelandclinic.org/health/articles/10132-menstrual-cycle

[5] https://my.clevelandclinic.org/health/diseases/21698-anovulation

[6] https://www.ncbi.nlm.nih.gov/books/NBK279054/

[7] https://my.clevelandclinic.org/health/body/22525-gonadotropin-releasing-hormone

[8] https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/ 

[9] https://www.ncbi.nlm.nih.gov/books/NBK441996/

[10] https://byjus.com/question-answer/what-is-a-graafian-follicle-in-the-ovary/

[11] https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/graafian-follicles

[12] https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00416-4/fulltext

[13] https://advancedfertility.com/infertility-testing/antral-follicle-counts/

[14] https://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics

[15] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882969/

[16] https://my.clevelandclinic.org/health/diseases/21698-anovulation

[17] https://www.ncbi.nlm.nih.gov/books/NBK279054/

[18] https://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics

[19] https://www.verywellhealth.com/oligoovulation-2616419 

[20] https://www.merckmanuals.com/professional/gynecology-and-obstetrics/infertility-and-recurrent-pregnancy-loss/ovulatory-dysfunction

[21] https://pmc.ncbi.nlm.nih.gov/articles/PMC9168655/

[22] https://www.sciencedirect.com/science/article/pii/S0015028217300602

[23] https://pmc.ncbi.nlm.nih.gov/articles/PMC4426152/

[24] https://my.clevelandclinic.org/health/diseases/22284-hyperprolactinemia

[25] https://pubmed.ncbi.nlm.nih.gov/30621143/

[26] https://www.cancer.org/cancer/types/pituitary-tumors/detection-diagnosis-staging/signs-and-symptoms.html

[27] chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.anncaserep.com/open-access/diagnosis-of-cushing-syndrome-during-an-infertility-evaluation-4555.pdf

[28] https://pmc.ncbi.nlm.nih.gov/articles/PMC4950431/

[29] https://www.yourhormones.info/endocrine-conditions/sheehans-syndrome/

[30] https://www.hopkinsmedicine.org/health/conditions-and-diseases/thyroid-disorders-in-women

[31] https://womenshealth.gov/a-z-topics/hashimotos-disease

[32] https://www.sciencedirect.com/science/article/abs/pii/S2213858719303456