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INTRODUCTION Normal Physiology

All women have two ovaries, which are located in the pelvis alongside the uterus. At birth the ovaries are provided with thousands of eggs. So the ovaries are like "banks" of eggs – unlike the testes in men, which manufacture sperm continuously from puberty on. At puberty the ovaries contain about 150 -300,000 eggs. Each month, under direction from the pituitary gland in the brain (which releases a hormone called Follicle Stimulating Hormone or FSH which stimulates the ovaries), a number (or "cohort") of these eggs are "recruited" to develop. Until this time the eggs had remained dormant in the ovary, but now they start to grow, each one in a little blister of fluid called a follicle, (follicles are also sometimes called cysts, in that a "cyst" is a structure containing fluid, and hence a follicle is a type of cyst).

Hundreds of eggs respond to the call, but most of them die (or become "atretic") within a couple of days. As you can see, hundreds of eggs from the "bank" are wasted every month.

By some process that we don't really understand, one follicle (very occasionally two) becomes "dominant" and continue to grow and mature, reaching a size of about 20 mm (or 2 cm). During its growth the cells, which line the follicle release a hormone called estrogen. Estrogen is the dominant female hormone and is responsible for many functions, including sexual characteristics like breast development, vaginal lubrication and, importantly, for stimulating the lining of the uterus (the "endometrium") to grow and prepare for a possible pregnancy. As the dominant follicle grows the estrogen levels in the bloodstream increase. This process of follicle growth is called "folliculogenesis".

The brain recognizes when the follicle is mature and sends another message to the ovary and follicle by way of a hormone called luteinizing hormone (or "LH"), which triggers the final maturation of the egg and then makes the follicle rupture and release the egg.

Hopefully the egg is "picked" up by the fallopian tube and it travels down the fallopian tube to the site of fertilization in a region called the ampulla. If at this time sperm were to enter the uterus, they would travel up the fallopian tube, and if a sperm fertilizes the egg an embryo would be formed. The embryo then has to travel down the tube until it reaches the uterus where it would implant in the lining of the uterus – the endometrium- and grow into a pregnancy.

After the follicle has ruptured and released the egg a new type of cyst forms – the corpus luteum. The corpus luteum has the important function of manufacturing yet another hormone called progesterone, which acts on the endometrium and nourishes it. This is how the early embryo is nourished while it is growing in the endometrium. The corpus luteum has a life span of only 14 days, after which – if no pregnancy occurs – it dies and disappears. When the corpus luteum dies it obviously stops producing progesterone, so the support for the endometrium is withdrawn, and the endometrium then dies and is shed. This is menstruation.

With menstruation hormone levels fall the brain realizes this and, once again, responds by releasing FSH to recruit the next cohort of dormant eggs. And so the whole cycle is repeated.

Obviously this is a very simplified explanation of things. It is also important to know that the ovary makes another type of hormone, which is called an androgen. Although this is a male hormone, it is produced in small quantities by the ovarian tissue in which the eggs lie waiting. Normal ovarian function relies on a perfect balance between these three hormone groups – estrogen, progesterone and androgen.

POLYCYSTIC OVARIAN SYNDROME (PCOS)

PCOS is a common condition and around one-in-five women have polycystic ovaries as defined by ultrasound. About 5–10% of women will have symptoms of this syndrome, which may include menstrual irregularities, acne, excessive hair growth and infertility.

At the start of a cycle many eggs respond to the messages being sent from the brain (i.e. FSH). Whereas normally a number of follicles would start developing but most die, leaving only one to grow to maturity, in PCOS many follicles continue to grow but do not develop to full maturity. After growing to an intermediate stage of development they stop: but they do produce estrogen, and the rising estrogen levels make the brain think that a follicle is ready to release. But there is no mature follicle ready to release an egg. The reason the estrogen levels are high is because there are many follicles making estrogen, and hence the brain "thinks" that a follicle is ready. The brain therefore causes the release of LH – but, because there is no mature follicle, no egg is released. However, the LH stimulates the ovarian tissue to release more androgens (the male hormone), which further upsets the balance and can result in excessive hair growth and acne. This situation continues, and the estrogen levels remain high, no follicles mature, no eggs are released, and the male hormone levels remain high. The high estrogen levels stimulate the endometrium to grow, and it gets thicker and thicker until, eventually, it outgrows its blood supply and breaks down and is lost. Such a menstrual bleed is not a well orchestrated one, and can be irregular and heavy.

On ultrasound these ovaries have numerous small follicles – hence the name Polycystic Ovarian Syndrome. These small follicles are typically just beneath the surface of the ovary – and on ultrasound appear like a "ring of pearls". Blood tests show higher than normal levels of estrogen and high levels of LH.

Patients who are overweight may be more predisposed to PCOS. This is because fat tissue tends to increase the blood levels of estrogen , thereby contributing to the hormone imbalance which leads to PCOS. In fact, obesity is a feature in about 2/3 of women with symptomatic PCOS.

Another important imbalance to understand is that of Insulin Resistance. Insulin is a hormone produced by the pancreas to regulate sugar levels. When sugar levels go up, like after a meal, more insulin is released. But in patients who are overweight and in patients with PCOS there appears to be a resistance to insulin. In other words, more insulin needs to be produced to keep the sugar level under control. Higher insulin levels stimulate the ovarian tissue to make androgens, which upsets the normal hormone balance and leads to PCOS. Insulin Resistance can also lead to diabetes and hypertension. Among the approximately 40% of subfertile women who have a disturbance of ovulation, PCOS is the most common cause.

DIAGNOSIS

In the majority of cases the diagnosis of PCOS is made from taking a woman's medical history and performing a clinical examination. Such women tend to complain of irregular periods, hair growth, acne, infertility and a chronic watery discharge. (The high estrogen levels stimulate the cervix to produce mucus which discharges from the vagina.) Physical findings on examination may include high blood pressure, obesity, hair growth, acne, watery vaginal discharge and sometimes a skin condition called "Acanthosis Nigricans". This skin condition is related to high insulin levels – and results in a velvety brown discolouration occurring at the base of the neck, under the breasts, in the armpits and on the inner thighs.

Blood tests might show higher levels of LH and testosterone (as well as other androgens). Ultrasound may show the "string of pearls" sign. Because PCOS is associated with diabetes and high cholesterol levels these can be tested too, usually by checking a fasting blood sugar and lipid profile. If the fasting glucose is greater than 7.8 mmol/l then a "glucose challenge test" is done.

website: www.pcosupport.org