Polycystic Ovarian Syndrome

 Polycystic Ovarian Syndrome(PCOS) is a condition affecting women in the child-bearing years which has some or all  of the following features :

• Excessive male hormone effects known as hyperandrogenism. This commonly appears as excessive body hair(including hair around the nipples and a “snail trail” in the centre of the lower abdomen), acne or male-pattern baldness type of hair loss from the scalp.
• Infrequency of menstrual periods or total loss of periods
• Multiple cysts on the ovaries(polycystic ovaries) as shown by ultrasound
• Obesity
• Impaired glucose tolerance(blood sugar levels which are higher than usual when tested with a Glucose Tolerance Test, but are not in the diabetic range. Impaired glucose tolerance often progresses to become type 2 diabetes)
• Fatty liver with elevated liver enzymes which is not due to alcohol
• Infertility or reduced fertility due to lack of ovulation requiring assistance in falling pregnant using fertility medications such as Clomiphene.

1. Lack of ovulation or infrequent ovulation( known as chronic oligo-ovulation)

2.Excessive male hormone effects such as acne, excess body hair or scalp hair loss

3. Polycystic Ovaries as demonstrated by ultrasound

PCOS is diagnosed by history  which reports infrequent or total loss of periods and complaints of excess body hair, acne or head hair loss, clinical examination which confirms features of excess male hormones(“snail-trail” on abdomen, hair around nipples, acne and possibly male-pattern baldness) combined with blood tests which show raised male hormones and ultrasound to demonstrate multiple cysts on the ovaries.

 Blood tests may also show high LH (luteinising hormone), high blood sugar levels, elevated liver enzymes and elevated triglycerides and cholesterol, although these features are not required for diagnosis. 

PCOS is a common disorder affecting 5-10% of women more than half of whom are overweight or obese. It is associated with an increased risk of type 2 diabetes (Ehrmann et al., 1999 ; Legro et al., 1999  and Metabolic Syndrome.  Type 2 diabetes in the United States is 10 times more common in young women with PCOS  as among normal women. Impaired glucose tolerance or  type 2 diabetes develops by the age of 30 years in 30 to 50% of obese women with  PCOS.  Metabolic Syndrome is two to three times more common among women with PCOS as among normal women corrected for body-mass index, and 20% of women with the polycystic ovary syndrome who are younger than 20 years of age have the metabolic syndrome. .(Nestler 2008) Obesity, particularly of the abdominal type, is present in varying degrees in women with PCOS (ranging from 10–50%).

It is thought that the raised blood sugar and insulin levels are responsible for the increased male hormones and loss of ovulation.

Women with PCOS are also thought to be at increased risk for endometrial cancer(cancer of the lining of the uterus) through ongoing lack of ovulation with excess estrogen exposure of the uterus without progesterone. Endometrial cancer has been shown to develop when oestrogen is not balanced by progesterone. However  evidence to support increased incidence of endometrial cancer in women with PCOS is limited (Hardiman et al., 2003 ). Standard practice to prevent endometrial cancer in  women who do not ovulate is either to induce  bleeding with a progestin every 1 to 3 months or to provide treatment with an oral contraceptive pill.

About half of women with the polycystic ovary syndrome  have  fatty liver disease which is not due to alcohol. This is manifested by elevated liver enzymes and the presence of increased fat with ultrasound. These women have greater abnormalities of sugar levels and are more likely to have the Metabolic Syndrome than patients with the PCOS who do not have liver abnormailities.  Fatty liver also appears to be involved in the development of heart disease. 

 Appetite regulation, as measured by subjective short-term hunger and satiety and ghrelin (a hormone involved in appetite regulation)levels, may be impaired in PCOS(Moran et al 2004)

Treatment of Polycystic Ovarian Syndrome

PCOS is treated firstly with a low calorie weight loss diet combined with a structured exercise program. A low calorie diet in overweight patients has been show shown by researchers to normalize the menstrual cycle, return ovulation/fertility to normal and alleviate features of male hormone excess. (Crossignani et al,2003)

 A structured exercise program has also been shown to improve fertility in obese PCOS patients. (Palombo, 2008)Women with PCOS should maintain a diet that is patterned after the type 2 diabetes diet. This diet includes an increase in fiber and a decrease in refined carbohydrates, as well as a decrease in trans and saturated fats and an increase in -3 and -9 fatty acids. Foods that contain anti-inflammatory compounds (fiber, -3 fatty acids, vitamin E, and red wine) should also be emphasized.(Liepa 2008) 

If diet and exercise are ineffective, a number of medications are available for use in treating this disorder. The most commonly used are Metformin, an anti-diabetic medication which has had success at normalizing blood sugar and insulin and returning the menstrual cycle to normal. Metformin improves insulin sensitivity and has been shown to retard or prevent progression to type 2 diabetes in patients with impaired glucose tolerance.

Flutamide is an anti-androgen which has been effective in treating excess body hair. De Leo and coworkers treated women with PCOS with fluatmide 250mg twice daily for 6 months and found excess body hair reduced significantly, male hormone levels dropped, and ovulatory cycles were restored in all subjects. Ultrasonographic examination in follicular phase showed a significant reduction in ovarian volume and ovaries of normal appearance.(De Leo et al 1998)

Gambineri and co-workers assessed the effects of a low-calorie diet plus Metformin 850mg twice daily and flutamide 250mg in a placebo-contolled trial and found metformin effective in normalizing the menstrual cycle and flutamide effective at reducing excess male hormone and reducing abdominal fat, including liver fat.Another commonly used medication is Spironolactone, which is most effective at reducing excess body hair. This effect is not instant and a trial of six months treatment should be allowed to see its effects.

 Women who do not wish to become pregnant can be effectively treated for excess body hair with specific oral contraceptives. Oral contraceptives containing non-androgenic progestins slow hair growth in 60-100% of women with elevated male hormone levels. Therapy can be started with a preparation that has a low dose of estrogen and a nonandrogenic progestin. Preparations that have norgestrel and levonorgestrel should be avoided because of their androgenic activity.

Women aiming for pregnancy are frequently treated in the short term with clomiphene, to induce ovulation and attain pregnancy.Menstrual irregularity can be treated with an oral contraceptive in those women seeking contraception.

REFERENCES

Cerda C, Pérez-Ayuso RM, Riquelme A, et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. J Hepatol 2007;47:412-417Vincenzo De Leo, Danila Lanzetta, Donato D’Antona, Antonio la Marca, and Giuseppe MorganteHormonal Effects of Flutamide in Young Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., Jan 1998; 83: 99 - 102.Pier Giorgio Crosignani¹, Michela Colombo, Walter Vegetti, Edgardo Somigliana, Alessio Gessati and Guido Ragni Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet
Hum. Reprod., Sep 2003; 18: 1928 - 1932 Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK and Imperial J (1999) Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 22,141–146. Gambarin-Gelwan M, Kinkhabwala SV, Schiano TD, Bodian C, Yeh HC, Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Clin Gastroenterol Hepatol 2007;5:496-501. [CrossRef][ISI][Medline]  Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003;361:1810-1812Legro RS, Kunselman AR, Dodson WC and Dunaif A (1999) Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 84,165–169Polycystic Ovary Syndrome (PCOS) and Other Androgen Excess–Related Conditions: Can Changes in Dietary Intake Make a Difference?
George U. Liepa, Aditi Sengupta, and Danielle Karsies
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Hum. Reprod., Mar 2008; 23: 642 – 650 The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-47Setji TL, Holland ND, Sanders LL, Pereira KC, Diehl AM, Brown AJ. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1741-1747Targher G, Arcaro G. Nonalcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007;191:235-240.