Polycystic Ovary Syndrome (PCOS)

If you are experiencing problems with your periods, having unexplained symptoms or have already been diagnosed with Polycystic Ovary Syndrome (PCOS), it helps to have an understanding of the condition to ensure you have the correct diagnosis and the right treatment. In this section, we explain the fundamentals of PCOS and take a closer look at:

• What is Polycystic Ovary Syndrome (PCOS)?
• What are polycystic ovaries?
• Underlying features of PCOS
• Diagnosing PCOS
• Investigations for PCOS
• What causes PCOS?
• Treatment for PCOS
• Irregular periods
• Skin problems
• Metformin for blood sugar control
• Anovulation (when you are not ovulating)
• PCOS, Weight & Metabolism
• PCOS and fertility
• Medical treatment to help ovulation
• Take-home messages if you have PCOS

What is Polycystic Ovary Syndrome (PCOS)?

Polycystic ovary syndrome (PCOS) is the commonest hormonal disturbance in women and is the main cause of problems with periods and ovulation. It is also the cause of 85–90 per cent of cases of anovulatory infertility. Aside from menstrual cycle disturbances (irregular or absent periods), the most significant problems if you have PCOS are difficulty in controlling body weight and skin problems (acne and unwanted hair growth on the face or body). Not all women with PCOS experience all of the symptoms and many will have relatively mild symptoms. If you have PCOS, the problems you experience may change over time. In particular, gaining weight can make PCOS symptoms worse.

If you have some of these problems and haven’t had a diagnosis, it’s important to be investigated for PCOS. This will involve an ultrasound scan and blood tests. It’s possible to have polycystic ovaries, as seen on ultrasound scan, without the full-blown syndrome. This happens in around 20–30 per cent of women whereas a smaller proportion will have symptoms of PCOS – perhaps 10–15 per cent. This does depend on where you come from, as there are worldwide and ethnic variations in the prevalence of the syndrome.

What are polycystic ovaries?

Polycystic ovaries contain many small follicles (incorrectly termed ‘cysts’) which each contain an egg and have started to grow, but do not reach a mature size and instead remain at a size of about 2–5mm in diameter. The diagnosis is best made by an ultrasound scan which visualises the ovaries and the small cysts within them. A polycystic ovary usually contains at least 20 of these small follicles or cysts and with modern ultrasound machines many more may be visible (these days we expect to see at least 20 per ovary, while a few years ago the diagnosis was made when 12 were seen). Sometimes blood tests show changes in hormone levels, although these changes are not universal and can vary considerably from person to person.

Underlying features of PCOS

Features of PCOS include:

• Androgen excess – elevated androgens (“male” hormones such as testosterone)
• Low oestrogen relative to testosterone
• High oestrogen relative to progesterone – this can lead to problems sustaining a pregnancy even if ovulation and fertilisation do occur
• Insulin resistance – when your body’s normal control of blood sugar by insulin becomes faulty
• Inflammation
• High Anti-Müllerian hormone or AMH – the hormone produced by the high number of developing follicles (“cysts”) in the ovaries

These features can result in:

• Unwanted hair growth
• Alopecia
• Acne
• Irregular or absent periods and/or anovulation
• Difficulties conceiving
• Weight gain
• Increased risk of other health complications
• Increased sensitivity to factors such as vitamin D deficiency in fertility treatment outcomes
• Reduced egg quality

Many of these features can be improved by changes to diet and lifestyle. We cover the best approaches in our Fertility and Preconception Care course, which includes a module on PCOS.

Diagnosing PCOS

If you have a scan, the ultrasound picture is not always clear. Some women with PCOS may have an ultrasound scan that does not clearly demonstrate polycystic ovaries. This isn’t a problem as the syndrome is defined by the presence other characteristics. In order to be diagnosed with PCOS, you must have at least two out of three of the following:

1. Signs or symptoms of high androgen hormones – predominantly testosterone – namely, unwanted facial or bodily hair, loss of hair from the head, acne or an elevated blood level of testosterone itself. If the testosterone is much higher than expected additional tests may be performed to look for other causes of androgen excess, for example tumours of the ovaries or adrenal glands and other rare hormonal conditions (such as late-onset congenital adrenal hyperplasia or Cushing’s syndrome).
2. Irregular or absent menstrual periods, after other causes for these have been excluded by simple blood tests to measure the other hormones – follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, prolactin and thyroid function.
3. Polycystic ovaries on an ultrasound scan.

Women with the full polycystic ovary syndrome may have high levels of:

• Testosterone: an ovarian androgen hormone that influences hair growth and is also converted to oestrogen.
• LH: a pituitary hormone which influences hormone production by the ovaries and is important for normal ovulation.
• Oestrogen (oestradiol): an ovarian hormone that stimulates growth of the womb lining (endometrium).
• Insulin: a hormone that is principally involved in the utilisation of energy from food, which when elevated may stimulate the ovary to overproduce testosterone and prevent the follicles from growing normally to release eggs and hence cause the ovary to become polycystic. Indeed, it is high levels of insulin that is thought to be one of the main problems for women with PCOS. Insulin becomes more elevated in women who are overweight. Insulin in the blood is not routinely measured, but often other signs of problems of insulin action are (see below).
• Anti-Müllerian hormone (AMH): a measure of the ovarian reserve (or how fertile the ovaries are) and correlates with the number of small follicles seen on the scan.

There are also many other subtle hormonal abnormalities that may affect ovarian function and influence the menstrual cycle, fertility, bodily hair growth, body weight and general health.

Investigations for PCOS

In order to test to see whether you have PCOS, the standard hormone blood tests include measurements of the following hormones:

• Testosterone
• LH
• FSH
• Thyroid hormones
• Prolactin

Other tests that are sometimes used are:

• Sex hormone binding globulin (SHBG) – the protein that carries testosterone around the blood.
• AMH

Other non-hormonal blood tests used for investigating PCOS include:

• Glucose tolerance test – a sugary drink – is given first thing in the morning on an empty stomach and blood taken at the time of the drink and then again after two hours. This helps to see how well the body handles sugar in food and is a screening test for diabetes. In essence it helps to assess the action of insulin
• HbA1c ( (glycosylated haemoglobin) is another way of assessing the long-term effects of blood sugar levels and is also used to screen for diabetes and monitor the long-term control of diabetes.
• Cholesterol levels (best done first thing in the morning before anything is eaten or drunk) – a useful indicator of long-term health, especially for women with PCOS who are overweight.

The other main important investigation for PCOS is an ultrasound scan of the pelvis to look at the ovaries and also the womb – it is important also to measure the thickness of the womb lining (endometrium), for reasons explained below.

What causes PCOS?

It is now thought that having polycystic ovaries may run in families and so there is some evidence of a genetic cause, although there are probably a number of genes involved, and for a condition that is so common there are likely to be a number of genetic and environmental influences for the development of PCOS. Some women may have polycystic ovaries and never have symptoms – or, for that matter, never know that they have polycystic ovaries. Ovaries do not suddenly become polycystic, but women who have polycystic ovaries may develop symptoms at any time, for reasons that are not always clear. Again in body weight is often the precipitating cause for the development of symptoms. The appearance of polycystic ovaries does not tend to disappear, although symptoms may improve, either naturally or as a result of therapy.

It appears that one of the fundamental problems is with overproduction of insulin due to inefficient handling of energy from food. While the extra insulin is working hard, it doesn’t turn carbohydrates from food into energy efficiently and instead they are turned into fat. The high level of insulin has other effects in the body, including stimulating the ovaries to overproduce androgens (mainly testosterone). This in turn prevents normal ovulation and also leads to longer term effects, such as the development of type 2 diabetes, high cholesterol levels and an increased risk of cardiovascular disease (heart attack and stroke).

The balance of hormones is affected by body weight and being overweight can greatly upset this balance and make the symptoms of PCOS worse. Being overweight is commonly associated with PCOS and this increases the risk of heart disease and high blood pressure in later life. Smoking cigarettes seriously worsens the risk of developing longer-term health problems associated with PCOS. Another problem sometimes seen over time is the development of ‘late-onset’ or type 2 diabetes, in which blood sugar levels stay abnormally elevated. In this event, it is then necessary to modify the dietary intake of carbohydrates and sometimes to take medication. The risk of both cardiovascular disease and diabetes can be reduced by keeping to the correct weight for your height.

The small cysts in the ovaries do not get larger, in fact they eventually disappear and are replaced by new cysts. The cysts (follicles) are on average 2–5mm and no greater than 9mm. If a follicle starts to grow and develops into a mature follicle it should then ovulate when it is about 20–25mm in diameter. Ovulation may occur regularly, for example once a month in women with PCOS who have regular periods, or less frequently in those with long gaps between their periods. The cysts are not the type of ovarian cyst that require surgical removal – such cysts are usually 50mm or larger and often have a different appearance. Furthermore, the cysts of the polycystic ovary do not lead to ovarian cancer.

Women with PCOS and infrequent or absent periods are at risk of excessive growth of the endometrium as a result of constant stimulation by oestrogen in the absence of progesterone, which is only produced by the ovaries after ovulation. It is important that the endometrium is shed on a regular basis to prevent this from happening as, if the endometrium becomes too thick, it may sometimes develop into cancer of the womb (endometrial carcinoma). The endometrium can be seen on an ultrasound scan and if it appears too thick or irregular, a hysteroscopy and endometrial biopsy procedure is advised in order to examine the endometrium under a microscope.

Treatment for PCOS

New global guideline for PCOS recommends lifestyle as the first-line intervention for the treatment of women with PCOS. A healthy diet is also extremely important if you have PCOS and should be the foundation for managing symptoms, including infertility and problems with ovulation. Exercise is also effective in improving symptoms including helping to regularise your periods.

Once you have these important foundations in place, there are medical treatments available if you are still experiencing problems with different aspects of your health.

Irregular periods

If you have PCOS, you may experience different symptoms at different stages in your life and may require treatments including if you are trying for a baby. Irregular and unpredictable periods can be very challenging and make life difficult. It also means you are likely to be also having irregular ovulation, which can make getting pregnant harder. It also poses the risk of your endometrium thickening. The longer the intervals between periods, the more likely they are to be heavy due to the increasing build-up of the endometrium. If you’re not trying to conceive, the a low-dose combined oral contraceptive (a contraceptive pill) is often prescribed. This will result in an artificial cycle and regular shedding of the endometrium. Some women cannot take the pill and need alternative hormonal therapy to induce regular periods, such as a progestogen/progesterone for ten days every one to three months, depending on individual needs.

We believe that it is important to have a period at least once every three to four months to prevent abnormal thickening of the womb lining. An alternative is to use a progesterone secreting coil (for example, a Mirena intrauterine system) which releases the hormone progesterone into the womb, thereby protecting it and usually resulting in reduced or absent menstrual bleeding.

Skin problems

If you have high androgen (testosterone) levels, the skin may be affected. Acne may appear on your face, chest or back. Sometimes there is also unwanted hair growth on the face, chest, abdomen, arms and legs. These problems may be more prominent in women with darker hair or skin, simply because the unwanted hair is more noticeable than in fairer people. There are also ethnic differences in the way the hair follicles respond to the hormones. A less common problem is thinning of hair on the head, although if this occurs it is rarely serious. Being overweight probably causes the worst problems for women with PCOS by aggravating imbalances of the hormones that control ovulation and affect skin and hair growth.

Physical treatments to remove unwanted hair, such as electrolysis, laser therapy and waxing, may be helpful while waiting for medical treatments to work, and are the only real options for women who wish to conceive as drugs are either contraceptive or dangerous for the developing baby. Electrolysis and waxing may be expensive and should only be performed by properly trained therapists as scarring can result from unskilled treatment. Shaving can help some women and, contrary to popular belief, does not make hair grow back faster.

Any combined oral contraceptive pill is likely to improve acne and unwanted hair growth by suppressing the production of testosterone from the ovaries and also raising SHBG levels, which mops up testosterone already in circulation. Some contraceptive medications contain specific anti-androgen hormones, such as cyproterone acetate and drospirenone, although they don’t appear to be much better in controlling the symptoms of PCOS. Spironolactone is an effective preparation, particularly for women who are overweight or who have high blood pressure (for whom the contraceptive pill may not be allowable). There are also other hormone treatments and drugs, such as isotretinoin, that can be effective, but also bring with them more potentially serious side effects and must not be taken when trying to get pregnant. Topical preparations such as eflornithine may be helpful, but also cannot be used while trying to conceive.

Metformin for blood sugar control

One treatment that has been popular in recent years is metformin. Because it lowers insulin, which causes some of the problems associated with PCOS, it was expected to improve symptoms. Initial studies appeared to be promising, suggesting that metformin could improve fertility in women with PCOS. However, more recent large trials have observed limited beneficial effects of metformin.

The role of metformin in the management of PCOS is therefore limited and you should only take it if you have impaired glucose tolerance. This is usually assessed by a glucose tolerance test or the measurement of HbA1c in the blood) or type 2 diabetes.

Anovulation

If PCOS is affecting your fertility even after you have made the appropriate dietary and lifestyle changes, there are various medical treatments available. We explain these in the IVF and Fertility Treatments section of The Fertility Guide.

PCOS, Weight & Metabolism

Being overweight worsens the symptoms of PCOS, yet it can be very hard to lose weight and there isn’t a simple solution. Having PCOS does not in itself make you gain weight, but women with PCOS find it easy to put on weight as their metabolism works inefficiently to deal with food. Regular physical exercise (at least 20–30 minutes of hard exercise, 5–7 days per week) will increase the body’s metabolism and significantly improve the ability to lose weight and improve long-term health.

Key points to be aware of if you suffer from PCOS:

• A healthy weight AND a healthy metabolism are important for fertility and reproductive health – especially for women with PCOS
• Being overweight worsens symptoms of PCOS and is often associated with the condition
• You can be slim and have a metabolic disorder and you can be overweight and malnourished
• Fat tissue is metabolically active and produces hormones including oestrogen
• Being overweight can contribute to a relative dominance of oestrogen over progesterone, which can lead to fertility problems and symptoms such a low mood, painful periods and PMS .

These aspects of the condition are specific areas that can be targeted through diet and lifestyle and something we cover in our courses. We routinely see improvements in symptoms including regularisation of the menstrual cycle, return of ovulation, weight loss and natural conceptions when these changes are made.

PCOS and fertility

Having PCOS can make it more difficult to get pregnant. There are various factors that influence how well the ovaries function and how much fertility may be affected depends on individual symptoms. Being overweight generally makes the condition worse and is one factor that increases the risk of infertility if you have PCOS. The first-line approach is therefore lifestyle changes and weight loss. Some women may continue to experience problems with ovulation and, if weight loss and lifestyle changes don’t help, there are medical treatments available to help induce ovulation.

Medical treatment to help ovulation

The first medical treatment to help with ovulation is drug-based therapy and the first drug to try is usually either letrozole or clomiphene citrate (both come as tablets). If you still don’t ovulate, the next stage is gonadotrophin therapy. Gonadotrophins are hormones that act on the gonads (ovaries and testes) and treatment with these hormones involves daily injections that contain predominantly FSH but also often LH too. The injections are subcutaneous – just under the skin – and so are quite easy to self-administer. If you have PCOS and you don’t respond to clomiphene, an alternative to gonadotrophin therapy is an operation known as laparoscopic ovarian surgery. This is laparoscopic (‘keyhole’) surgery where the ovaries are cauterised (a small hole is made using heat – called ovarian diathermy or ‘drilling’). This, strange as though it may sound, can help re-start ovulation. Although ovarian diathermy appears to be as effective as gonadotrophin drugs in the treatment of women with PCOS who do not respond to first-line therapy, it does take longer to get pregnant. Around half of those treated still need drugs to stimulate ovulation (either clomiphene or gonadotrophin injections). You are more likely to respond better to laparoscopic ovarian diathermy (LOD) if you are slim with high LH levels.

If you haven’t conceived after between six and nine monthly treatment cycles with drugs to help you ovulate, then there are likely to be other things preventing you getting pregnant aside from not ovulating. The next step in your treatment is therefore in vitro fertilisation (IVF).

As with ovulation induction, if you have polycystic ovaries, the response to stimulation will be very different from that of normal ovaries. IVF depends on inducing many follicles to grow, and the polycystic ovary tends to have a more ‘explosive’ response with the development of lots of follicles in response to stimulation, which is associated with very high levels of circulating oestrogen. In some cases, this may result in ovarian hyperstimulation syndrome (OHSS), which is more common in women with polycystic ovaries. This is a serious, potentially life-threatening complication, so treatment of women with PCOS needs to be carefully managed.

Take-home messages if you have PCOS

PCOS is a lifelong condition that can affect many aspects of your physical health, wellbeing (including emotional wellbeing) and quality of life. Having a good understanding of the condition and knowing what you can do both in terms of dietary and lifestyle changes that you can manage yourself and ensuring you are receiving the best medical treatments can make a huge difference in helping you to manage the condition effectively.

References

1. Adam Balen and Grace Dugdale. The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy. Penguin Random House (Vermilion) 2021
2. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018 Aug;110(3):364-379.
3. Sharpe, A., Morley, L. C., Tang, T., Norman, R. J., & Balen, A. H. (2019). Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews, (12).

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