PCOS – the how, why & buts
Friday, 6 May 2022
There are many misconceptions about PCOS, the first being it’s name. Despite it’s given term; polycystic ovarian syndrome, having cysts on the ovaries is not what is happening. Instead, what is actually being observed on an ultrasound are underdeveloped follicle sacs in which eggs develop.
Normally, ovarian follicles containing egg cells are released at ovulation. In PCOS, the production of abnormally high levels of androgens (male hormones) prevent follicles from maturing to release egg cells. Instead, these immature follicles accumulate in the ovaries - they are not cysts!
What causes the production of abnormal androgen levels?
In a “normal” (approx 28 day) cycle, the hormone progesterone, produced after ovulation (approx day 19 onwards) exerts an inhibitory feedback mechanism that slows the release of luteinising hormone (LH). In PCOS this feedback is decreased or absent, resulting in a chronic & higher LH production. The theca cells (in the ovaries) LOVE LH and once activated over produce androgens.
There are two cells in the ovary that contribute to oestrogen production and they work synergistically. The theca cell converts cholesterol to two androgens (androstenedione and testosterone) under the influence of LH.
These androgens then travel through the basement membrane into the granulosa cell which, under the influence of FSH, converts them to oestrogen via a process called aromatisation.
Excess LH stimulation then will generate more androgens and the ovary has a hyperandrogenic milieu.
An overproduction of androgens, results is symptoms such as erratic menstrual cycles, missed periods unpredictable ovulation and more.
Symptoms of androgen excess in women are:
What is YOUR main cause of androgen excess in PCOS. First, spoiler alert - if you don’t have an excess of androgens on a blood test (free testosterone) then you do not have PCOS! So, what are the main drivers of excess production of androgens that produce symptoms as above?
The central mechanism is an abnormally higher release of luteinising hormone (LH) from the pituitary that causes the theca cells (in the ovaries) to over produce androgens
Insulin resistance: Increased insulin levels cause the ovaries to make & release male hormones (androgens). Insulin also lowers Sex Hormone Binding Globulin levels - making more free testosterone available
Low-grade chronic inflammation: leads the immune system to produce chemicals which contribute to insulin resistance, stimulating the ovaries to make too much testosterone!
Activation of more potent testosterone to dihydrotestosterone (DHT): Inflammatory chemicals and a low SHBG activate an enzyme 5-alpha reductase to convert testosterone to the far more potent version DHT
Finally, if you are taking the Oral Contraceptive, give some thought to what type you are on. Certain brands of the pill are high in androgens and it's not uncommon to have a testosterone surge when coming off them. Brands like Yasmin, microgynon, ovranette and cerazette.
The final component – I want to go back to the brain and explore the underlying brain-hormone mechanisms that contribute to ovulatory disturbances. And in the words of the artist Hot Chocolate, it starts with a kiss - or here a neuropeptide called Kisspeptin.
So, if we remember; in a “normal” cycle, progesterone excretes an inhibitory feedback mechanism that slows luteinizing hormone (LH) production. In PCOS this feedback is decreased or absent, resulting in a chronic LH production and stimulation of the ovaries to overproduce androgens.
The control & release of LH is managed by a cluster of neurons in the brain; which release pulses of the hormone - GnRH, a type of pulse generator system.
The pulse generator itself is regulated by a neuropeptide kisspeptin (and also GABA), and it goes like this…
So in a situation of high levels of androgens & anovulatory cycles the GnRH/LH pulses remain chronically high - LH acts on the ovarian theca cells to churn out more testosterone.
Brain-hormone mechanisms that contribute to ovulatory disturbances
The rate of the generator and GnRH pulses directly coordinates the secretion of FSH and LH, and therefore ebb and flow of oestrogen and progesterone across the menstrual cycle
What to do?