What is the link between PMOS and Hyperandrogenism (or Androgen Excess)?

According to the 2023 International Evidence-Based Guidelines for the Assessment and Management of PCOS, hyperandrogenism, a condition where an individual has elevated levels of androgens (commonly known as “male hormones”), is one of the core features of PMOS.

Between 60 and 100% of individuals with PMOS exhibit hyperandrogenism,[1] an excess level of androgens, a type of sex hormone.[2]  In this article we explore the link between PMOS and Androgen Excess.

PMOS is associated with abnormal functioning of the system of hormones that connects the hypothalamus, the pituitary and the ovaries (the “HPO axis”).[3]

The hypothalamus is an area of the brain that produces a variety of hormones, or chemical messengers, controlling body temperature, heart rate, hunger, mood, sex drive, sleep and thirst control as well as the release of hormones from a number of glands, especially the pituitary.[4]

The pituitary is a pea-sized gland at the base of the brain which is known as the “master gland” as it sends instructions to other cells in the body, including reproductive cells in the ovaries.[5]

The ovaries are oval-shaped organs located on either side of your uterus that store eggs and produce hormones that control the menstrual cycle and pregnancy.[6]

In individuals with PMOS, the activity level (pulse frequency) of one of the hormones produced in the hypothalamus, the Gonadotrophin Releasing Hormone (GnRH), is over-active.[7]

• Elevated levels of GnRH trigger 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;[8]

• Elevated LH levels lead to increased stimulation of theca cells, a type of cell within the ovary that plays an essential role in fertility;[9]

• 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,[10] to two androgens or sex hormones (androstenedione and testosterone);[11][12]

• 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;[13]

• 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;[14] and

• Some of these excess androgens are not converted and therefore lead to an androgen-rich environment within the ovary[15] and elevated levels of circulating androgens.

Hyperandrogenism can be caused by a range of other factors beyond PMOS.  Health conditions that can cause excess androgens include congenital adrenal hyperplasia (CAH), Cushing disease and androgen-secreting tumors.[16]  Certain medications, such as anabolic steroids, can also cause hyperandrogenism.[17]

CAH is a group of genetic disorders that affect that adrenal glands, a gland on the top of each kidney that produces a number of hormones.[18]  Cushing’s disease (a rare pituitary disorder) leads to overproduction of cortisol, the “stress hormone”, resulting in high glucose levels and the development of Type 2 diabetes.  Cushing syndrome is a side-effect to a type of medication called glucocorticoids and results in similar symptoms with high glucose and can also lead to Type 2 diabetes.[19]  Tumors that secrete excessive amounts of androgens, estrogens or a combination of these sex hormones are extremely rare.[20]

Hyperandrogenism can affect individuals assigned male at birth (AMAB) as well as those assigned female at birth (AFAB).[21]

Sources 

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683693/

[2] https://my.clevelandclinic.org/health/diseases/24639-hyperandrogenism

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

[4] https://medlineplus.gov/ency/article/002380.htm 

[5] https://www.healthdirect.gov.au/pituitary-gland 

[6] https://my.clevelandclinic.org/health/body/22999-ovaries 

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

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

[9] https://pubmed.ncbi.nlm.nih.gov/15833266/

[10] https://my.clevelandclinic.org/health/articles/23922-what-is-cholesterol 

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

[12] https://my.clevelandclinic.org/health/articles/22002-androgens      

[13] https://my.clevelandclinic.org/health/body/22528-granulosa-cells

[14] https://my.clevelandclinic.org/health/body/22353-estrogen 

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

[16] https://my.clevelandclinic.org/health/diseases/24639-hyperandrogenism

[17] https://my.clevelandclinic.org/health/diseases/24639-hyperandrogenism

[18] https://my.clevelandclinic.org/health/diseases/17817-congenital-adrenal-hyperplasia

[19] https://www.niddk.nih.gov/health-information/endocrine-diseases/cushings-syndrome

[20] https://columbiasurgery.org/conditions-and-treatments/sex-hormone-producing-tumor          

[21] https://my.clevelandclinic.org/health/diseases/24639-hyperandrogenism