Description

Polycystic ovarian disease is a condition in which there are an abnormally large number of small cysts on the ovaries. These cysts cause hormonal imbalances. As a results some or all of the following symptoms may be present:

  •        Acne
  •        Weight gain and trouble losing weight.
  •        Extra hair on the face and body. Often women get thicker and darker facial hair and more hair on the chest, belly, and back.
  •        Thinning hair on the scalp.
  •        Irregular periods. Often women with PCOS have fewer than nine periods a year. Some women have no periods. Others have very heavy bleeding.
  •        Fertility problems. Many women who have PCOS have trouble getting pregnant (subfertility).

Causes of PCOS

The exact cause is unknown, but it’s thought to be related to abnormal hormone levels, and is often associated with insulin resistance.

Resistance to insulin

Insulin is a hormone produced by the pancreas to control the amount of sugar in the blood. It works particularly on the liver and muscle cells, causing them to absorb more glucose from blood where it is either broken down to produce energy or converted to long term energy stores.

When someone is resistant to the effects of insulin, the blood sugar lowering action does not work properly and the body produces extra insulin.

Insulin has another effect; it causes the ovaries to produce testosterone. In most women this is within the normal range, but women with PCOS who have too much insulin may also produce too much testosterone. The raised levels of testosterone can give rise to some of the symptoms associated with PCOS, such as excess hair growth and head hair loss.

High levels of insulin and testosterone may also prevent the normal development of follicles in the ovaries, with many not developing fully. This causes problems with ovulation, so many women have period problems and reduced fertility.

Insulin resistance can also lead to weight gain. Excess fat causes the body to produce even more insulin which can make the symptoms worse. A vicious circle can result so it’s important to try to minimise weight gain.

Genetics

PCOS sometimes runs in families. Women who have close relatives – e.g. mother, aunt or sister – with PCOS are also more likely to be affected. This suggests there may be a genetic link, although specific genes have not yet been identified.

Inofolic

When taken at the recommended dose of 2 sachets per day, Inofolic provides 400mcg of folic acid (the recommended daily amount) and 4g of myo-inositol.

Myo-inositol is a natural substance found in every living cell that is essential for the correct functioning of insulin, enabling appropriate glucose metabolism.

A deficiency in this substance can cause insulin receptors to work less effectively. This deficiency is further compounded inside the cell where glucose metabolism is compromised.

As a result, less glucose is absorbed from the blood so that blood glucose remains high and this, in turn, causes the body to compensate by secreting more insulin.

There has been great deal of research in the last few years focussing on the role of myo-inositol (MI) in particular and our understanding of its importance is becoming clearer. It is essential that it is present in normal quantities in order for insulin to have its desired effect.

Recently, it has been suggested that many women with PCOS can be thought as having a genetically determined deficiency of MI. Supplementing such patients with Inofolic results in significant beneficial effects.

 The diagram below shows a schematic of how insulin and myo-inositol interact.


PCOS pic 1
Main biochemical and clinical benefits of Inofolic Significance (p)
Reduces systolic and diastolic pressure 0.002
Lowers plasma triglycerides by 52% and total cholesterol by 19% 0.001
Increases whole body insulin sensitivity by 84% 0.002
Lowers total testosterone by 65% 0.003
Enhances peak progesterone by 129% 0.003
Ovulation rate increased to 69.5% compared13with control group of 21% 0.001
Lowers hirsutism score and reduces severity of acne 0.003
Benefits during ART Significance (p)
Lowers overall dose of gonadotrophins 0.001
Greater number of oocytes of diameter 15mm during stimulation with significant reduction of immature oocytes 0.005
Benefits during pregnancy Significance (p)
Reduces incidence of gestational diabetes mellitus 0.001
Gestational age at delivery is 39.3 weeks vs control of 37.2 0.001
Curbs BMI increase from 3.8 in control to 2.3 in MI group 0.001

Very well tolerated

No side effects were reported in the six studies that were part of a systematic review of myo-inositol. These involved nearly 600 women where the treatment group received either 2 or 4 g of myo-inositol daily.

Only a very high dose of 12g or more per day induced side effects. These were mild gastrointestinal side effects such as nausea, flatus and diarrhoea. Severity did not increase with dosage which was raised to 30g/day in one study.

Treatments for PCOS

PCOS has a significant impact on physical, psychological and social health.  Treatment needs to be tailored according to the needs of the patient.

Weight Loss

  • Weight loss in overweight patients will help to reduce insulin levels and improve hormonal balance.  The ideal body mass index should be between 20 -25.  Many symptoms including acne and excess hair growth may improve with weight loss and a normal menstrual pattern with regular ovulation may recommence with this measure alone.
  • The most appropriate diet for women with PCOS is one that promotes more stable levels of blood sugar and lower levels of insulin.  A standard low fat high carbohydrate weight loss diet is not ideal.  High intakes of carbohydrates especially refined carbohydrates like sweets, white bread etc will quickly turn to sugar and cause elevated levels of insulin.  A low glycaemic index diet which will not cause a rapid rise in blood sugar is better for women with PCOS.
  • Carbohydrates should be spaced throughout the day to avoid peaks in blood sugar and insulin production.  Carbohydrates should be combined with proteins and/or fat rather than be eaten alone.  It is also best to avoid carbohydrates that trigger more hunger and cravings.
  • Drugs may be used to aid weight loss by either reducing gastrointestinal absorption of fats (Orlistat) or by suppressing appetite in the brain (Sibutramine) and bariatric surgery can be considered.

Hormone Treatments for irregular/absent periods

  • The combined oral contraceptive pill can be given to regulate the menstrual cycle and to reduce the risk of endometrial cancer.  The combined oral contraceptive pill supplies cyclical levels of oestrogen and progesterone and also increases the circulating level of sex hormone binding globulin (SHBG) which has the effect of inactivating androgens thereby reducing the symptoms of acne and excess hair growth.
  • Dianette is a hormone preparation that contains oestrogen and anti-androgen.  Dianette is an effective oral contraceptive pill but it is best not used solely for this purpose.  It can take a few months of treatment before symptoms of acne or hirsutism resolve and it is recommended that this medicine should be stopped three or four months after symptoms have resolved.

Metformin

  • Metformin is a drug that is normally used to treat Type II Diabetes.  The link between PCOS and insulin resistance is well established and using Metformin for this condition may help control the amount of glucose in your blood.  It may also decrease the amount glucose you absorb from your food and the amount of glucose made by your liver.  Patients may experience gastrointestinal side effects such as nausea, abdominal pain, flatulence and diarrhoea initially after commencing this treatment but the side effects normally disappear within two to three weeks.  These side effects may be minimised by taking the drug with food.

Other Anti-androgen treatments

  • Spironolactone is normally used for treatment of high blood pressure and fluid retention.  However it does have anti-androgenic activity and therefore can be used in women with acne and hirsutism (excess hair growth).  Due to the way Spironolactone works, only women whose acne has an hormonal basis will see improvements with this medication.  Some studies have found that 66% of women who took Spironolactone to have excellent improvement or complete clearing of the skin.  When used in combination with oral contraceptives this figure improves to 85%.

Topical preperations

  • Eflornithine cream (Vaniqua) is licensed for the treatment of facial hirsutism in women.  It irreversibly inhibits an enzyme (ornithine decarboxylase) involved in controlling hair growth and proliferation.  The treatment does not remove hair but slows down hair growth such that users require less frequent hair removal by other methods.  Eflornithine improves symptoms of hirsutism reduces darkening of facial skin and reduces associated psychological discomfort.  However once treatment stops hair re-grows to pre-treatment levels within eight weeks.  Many patients use Vaniqua in combination with other cosmetic treatments such as waxing, electrolysis and laser treatments.Treatment should normally be for six months only.  If conception has not occurred in this time consideration should be given to other treatments such as intrauterine insemination (IUI) or IVF treatment.Gonadotrophin therapy using follicle stimulating hormone is a more powerful way to induce ovulation but this should only be performed by specialists who can monitor the response to treatment.
  • Clomifene and gonadotrophin therapy are both associated with a twin pregnancy rate between 10 to 20%.
  • For women with PCOS who do not respond to Clomifene citrate, laparoscopic ovarian diathermy can be used.  This involves performing a laparoscopy and drilling holes in the ovary using a diathermy needle.  This may help to induce ovulation and 80% of couples for up to eight months following treatment.
  • Treatments to Improve Fertility
  • 
Clomifene citrate is a selective oestrogen receptor modulator that can be used to induce ovulation.  By blocking oestrogen receptors, more follicle stimulating hormone (FSH) is produced which promotes the development of follicles and therefore eggs within the ovary.  The first cycle of treatment should be monitored by ultrasound scan to confirm an adequate follicular and endometrial response.  Some patients over respond to therapy producing more than two follicles which gives a higher risk of developing higher order multiple pregnancy (triplets, quadruplets etc).