This blog will explain the process to ovulation, "folliculogenesis", before uncovering the differences in PCOS which can prevent ovulation (referred to as "anovulation").
At the start of a menstrual cycle, the ovary contains eggs. Each egg is surrounded by a coat of cells referred to as "follicles" which mature for ovulation.
The process of maturation of the ovarian follicles is called "folliculogenesis". This is essential for successful ovulation. This is because a dominant follicle is selected for ovulation as it homes a mature ovum for fertilisation.
"What is the process of folliculogenesis?"
Folliculogenesis involves the maturation of a primordial follicle to a primary, secondary, antral and preovulatory follicle. This is before the mature follicle releases the ovum into the fallopian tube for ovulation.
After the egg is released, a "corpus luteum" is formed from the remaining follicle. This secretes progesterone and oestrogen for the development of the uterine lining. The image below is a simplified outline of the development of a follicle.
"What hormones are essential for folliculogenesis?"
Two hormones are required for folliculogenesis, which are: luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH in synergy with FSH stimulates follicular growth and the production of oestrogen, both required for ovulation.
In early folliculogenesis, LH binds to the outer cell layer of follicles called "theca cells". Probably to your surprise, this causes the production of androstenedione and testosterone (but this is essential!). This is by an enzyme called CYP17.
Later in folliculogenesis, FSH acts on the inner cell layer of follicles called "granulosa cells". This activates an enzyme called aromatase which produces estrodial from the already made testosterone.
If you have been diagnosed with PCOS, or have an interest in this syndrome, a very important fact to know is that PCOS women have higher LH secretion compared to healthy women. This hormone is secreted from an area of the brain called the anterior pituitary.
"Why can having too much LH prevent ovulation in PCOS?"
It is hypothesised that increased LH stimulation on ovarian theca cells can disrupt folliculogenesis by two mechanisms.
"Abnormally high levels of testosterone disrupts folliculogenesis"
Firstly, the abnormal LH stimulation in early folliculogenesis produces a very high level of testosterone. This abnormal microenvironment reduces granulosa cell sensitivity to FSH, preventing the production of oestradiol. This is essential for the development of a mature follicle for ovulation. This arrests follicle development, essentially the "cysts" we see on an ultrasound.
2. "Abnormally high Anti-Mullerian Hormone (AMH) disrupts folliculogenesis"
To understand the second answer to this question, we should first discuss another interesting hormone called Anti-Mullerian Hormone (AMH).
AMH is secreted from the granulosa cells in the early stages of folliculogenesis. FSH has a role to decrease the AMH levels for the development of larger follicles from smaller follicles.
Recent scientific studies have found that LH correlates positively with AMH levels. Therefore, PCOS women have higher AMH levels, similar to their increased LH levels. High AMH levels in early folliculogenesis produces a microenvironment that reduces granulosa cell FSH sensitivity.
Therefore, alike the first hypothesize, PCOS women can not convert the extreme testosterone levels produced by LH stimulation to estrodial, preventing ovulation. This arrests follicle development, preventing the selection of a mature follicle for ovulation.
"Why do some PCOS women ovulate?"
I think this is a really important question that researchers like myself are very interested to understand. Stay tuned for more blogs on this topic!
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