Polycystic Ovary Syndrome (pcos) Review

Polycystic Ovary Syndrome (PCOS) is a complex endocrine metabolic disorder that affects how a woman`s ovaries work. It primarily involves ovarian hyperandrogenism and linked with insulin resistance. (Minerva Pediatrica, 2010) Associated with polycystic ovaries, menstrual dysfunction, anovulation, ovulatory dysfunction and other metabolic disturbances. Also known as Stein-Leventhal Syndrome.

PCOS affects between 8% and 20% of reproductive-age women worldwide. (Sirmans & Pate, 2014) Because there is no universal definition of PCOS, the exact number of women with PCOS is unknown. Most women are diagnosed during their twenties or thirties, but PCOS may affect girls as young as 11 who haven’t even had their first period. (National Center for Biotechnology Information, 2016) Menstrual disturbances commonly observed in PCOS include oligomenorrhea, amenorrhea, and prolonged erratic menstrual bleeding. ( Farquhar C, 2007) However, 30% of women with PCOS will have normal menses. (Balen, 1995)

Approximately 85%–90% of women with oligomenorrhea have PCOS while 30%–40% of women with amenorrhea will have PCOS. (Hart, 2007) Prevalence estimates for PCOS, as defined by the NIH/NICHD criteria, indicate that PCOS is a common endocrinopathy affecting 4%–8% of women of reproductive age. (J Clin Endocrinol Metab. 2004) Recently, several groups have demonstrated that the prevalence of PCOS varies depending on the diagnostic criteria used (see Table 2). (March et al, 2010-2012) These studies consistently report that the prevalence estimates using the Rotterdam criteria are two to three times greater than those obtained using the NIH/NICHD criteria.

Prevalence of polycystic ovary syndrome (PCOS) using different diagnostic criteria Source Population NIH/NICHD criteria ESHRE/ASRM (Rotterdam) criteria Androgen excess and PCOS society criteria:

March et al 728 Australian women 8.7% 17.8% 12.0%

Mehrabian et al 820 Iranian women 7% 15.2% 7.92%

Tehrani et al 929 Iranian women 7.1% 14.6% 11.7%

Yildiz et al 392 Turkish women 6.1% 19.9% 15.3%

Abbreviations: ESHRE/ASRM, European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine; NIH/NICHD, National Institutes of Health/National Institute of Child Health and Human Disease.

A family history of PCOS is a risk factor for PCOS. Based on the clustering of cases in families, PCOS is considered to be a heritable disorder. ( Franks et al, 1997) A high prevalence of PCOS or its features among first-degree relatives is suggestive of genetic influences. (Amato et al, 2004) In addition, greater concordance has been reported in monozygotic twins versus dizygotic twins. (Vink et al, 2006) However, the mode of inheritance remains elusive. Issues that hamper progress in this area include the heterogeneity of PCOS phenotypes, difficulty in assigning a phenotype to men, postmenopausal women, and prepubertal girls, and difficulties in obtaining large enough sample sizes to allow for adequate statistical power. (Goodarzi et al, 2011)

A genome-wide association study conducted amongst Han Chinese has identified loci on chromosomes 2p16.3, 2p21, and 9q33.3.(Chen et al, 2011) Some of these results were replicated in European cohorts, namely the chromosome 2p21 THADA and chromosome 9p33.3 DENND1A susceptibility loci. The sharing of the same susceptibility genes suggests that PCOS is an ancient disorder originating before humans migrated out of Africa. (Diamanti-Kandarakis et all, 2012)

An increased prevalence of PCOS is associated with a number of conditions. A history of weight gain often precedes the development of the clinical features of PCOS,(Isikoglu et al, 2007) and following a healthy lifestyle has been shown to reduce body weight, abdominal fat, reduce testosterone, improve insulin resistance, and decrease hirsutism in women with PCOS. (Moran et al, 2011) Obese women referred for assistance with weight loss had a prevalence of PCOS of 28.3%. (Alvarez-Blasco et al, 2006) However, in an unselected population, a prevalence of PCOS did not vary significantly based on obesity class. (Yuldiz et al, 2008)

PCOS prevalence rates for underweight, normal-weight, overweight, mildly obese, moderately obese, and severely obese women were 8.2%, 9.8%, 9.9%, 5.2%, 12.4%, and 11.5%, respectively. The authors concluded that obesity may increase the risk of PCOS but that the effect was modest.

Aetiology & pathophysiology

Main Causes and Risk Factors:

• Obesity andor insulin resistance.
• A family history of polycystic ovaries or metabolic disorders.
• Premature menarche.
• Premature adrenarche.
• Hyperandrogenism
• Type 1, 2, gestational DM.
• Antiepileptic drugs (for example, valproate)
• DENND1A gene is linked to PCOS in many populations.

The clinical, biochemical and diagnostic features of PCOS are known, yet the aetiology remains unknown (Elghblawi, 2007). Three-fourths of women with secondary amenorrhea meet the diagnostic criteria for PCOS (Hill, 2003). Women with PCOS are at risk for developing type 2 diabetes mellitus, hyperlipidaemia, reproductive system cancers, sleep apnoea and infertility problems (Ehrmann, 2005; Guzick, 2004; Sherif, 2006; Taylor, 1998).

Typically, PCOS symptoms first appear in adolescence, normally around the state of menstruation. Occasionally, some women do not develop PCOS symptoms until their early to mid-20s. One of the most common symptoms of PCOS is irregular periods. Polycystic ovary syndrome (PCOS) becomes symptomatic during adolescence and affects at least 5% of reproductive-age women. PCOS is a heterogeneous syndrome of unexplained chronic hyperandrogenism and oligo-anovulation, with a polycystic ovary being an alternative diagnostic criterion.

Clinical signs and symptoms

In addition to the three features used to diagnose polycystic ovary syndrome (PCOS) (absence of ovulation, high levels of androgens, and ovarian cysts), PCOS has many signs and symptoms, some of which may not seem to be related (American College of Obstetricians and Gynaecologists, 2015).

Menstrual irregularities:

• No menstrual periods – amenorrhea
• Frequently missed periods – oligomenorrhea
• Very heavy periods – menorrhagia
• Bleeding but no ovulation – anovulatory periods

• Infertility
• Hirsutism – excess hair growth on the face, chest, belly, or upper thighs
• Severe, late-onset, or persistent acne that does not respond well to usual treatments
• Obesity, weight gain, or trouble losing weight, especially around the waist
• Pelvic pain
• Cysts on one or both ovaries(not necessarily, only present in some patients)
• Oily skin
• Male pattern balding
• Acanthosis nigricans – patches of thickened, dark, velvety skin
• Anxiety & depression

Because many women don’t consider problems such as oily skin, extra hair growth, or acne to be symptoms of a serious health condition, they may not mention these things to their health care providers. As a result, many women aren’t diagnosed with PCOS until they have trouble getting pregnant or if they have abnormal periods or missed periods.

Differential diagnosis

Conditions that look like or may present in a similar way to PCOS are:

• Adrenal hyperplasia (excess hormone production by the adrenal glands)
• Problems with the function of the thyroid gland
• Hyperprolactinaemia (excess production of the hormone prolactin by the pituitary gland).

Health care providers look for three characteristic features of polycystic ovary syndrome (PCOS): absence of ovulation, high levels of androgens, and cysts on the ovaries. Having one or more of these features could lead to a diagnosis of PCOS. After ruling out other conditions and before making a diagnosis of PCOS, health care provider will do the following:

Take full family history. Patient`s menstrual cycle and any history of infertility, as well as whether there is a history of PCOS symptoms in a family.

Blood tests: Increased androgens(testosterone, androstenedione & DHEA-S), Low sex hormone binding globulin (SHBG), High LH: normal or low FSH, High oestrogen (oestradiol), Hyperinsulinemia & blood glucose levels.

Ultrasound to investigate the presence of 12 or more follicles in each ovary measuring 2 to 9 mm in diameter and/or increased ovarian volume.

Possibly laparoscopy

Orthodox medical treatment – goals:

1. Treat hyperandrogenic symptoms like acne and hirsutism.
2. Treat underlying metabolic disorders.
3. Prevent complications like hyperplasia or carcinoma.
4. Contraception for those who are not pursuing pregnancy.
5. Ovulation induction for those who are pursuing pregnancy.
6. Lifestyle modifications: diet, exercise for weight reduction.

Females not pursuing pregnancy:

• First line treatment is oestrogen-progesterone combined oral contraceptive pills 20 mcg. Benefits include endometrial protection, contraception, and control of hyperandrogenic symptoms.
• If the hyperandrogenic symptoms do not resolve after 6 months, antiandrogens can be added. For example, spironolactone 50 to 100 mg twice daily.
• Metformin to reduce insulin level.
• Statin to reduce cholesterol.

Ovulation induction:

• Clomiphene citrate as first-line therapy for non-obese women, if obese, then Letrozole is a choice.
• In vitro fertilization.

Natural medicine

Nutrition can play a huge part in a strategy of reversing PCOS, but there isn’t one best diet for it because there is no one PCOS. (Goodwin, 2017) PCOS is a syndrome which means that it’s a constellation of symptoms that are grouped together to make more sense of what’s going on (just like in irritable bowel syndrome, or chronic fatigue syndrome).

Majority of women with PCOS suffer from insulin resistance and that means that their body struggles to use carbohydrates for energy, and so instead stores them as fat, especially around the belly. In this case options like low carbohydrate/moderate protein/ high-fat diet might be considered (variations of keto and paleo diets tuned to an individual`s needs) in order to reverse insulin resistance. One more option to consider for reversing insulin resistance would be intermittent fasting. Natural remedies to support this process: Chromium, vitamin D, cinnamon, Gymnema. Other women with PCOS might not have insulin resistance, and may instead have high DHEA-S which shows that it’s her stress hormones that are the issue. So if we go too low carbohydrate for her, it’s going to make her worse. In this case, we would rather concentrate on improving the function of her adrenal glands.

Natural remedies: adrenal fatigue support nutrients might typically include Vitamins B5 and B12, Vitamin C, Magnesium, probiotics, and adaptogens such as ashwagandha, licorice root, and maca. Another thing to possibly concentrate on in PCOS patients is a treatment of chronic underlying inflammation in a body as well as establishing healthy gut flora and adequate mineral intake/absorption. All methods listed above can work really well in conjunction with standard orthodox medical care given that patient`s health situation has been properly researched and tested.

Prognosis

Most women with polycystic ovary syndrome produce excess androgens, a condition called hyperandrogenism. Having too much of these hormones typically leads to hirsutism, acne, and male pattern baldness.

Hyperandrogenism and abnormal levels of other sex hormones prevent ovulation and regular menstrual periods, leading to subfertility or infertility. For those who achieve pregnancy, there is an increased risk of complications and pregnancy loss. Due to irregular and infrequent menstruation and hormone abnormalities, affected women have an increased risk of endometrial cancer.

About half of all women with polycystic ovary syndrome are overweight or obese and are at increased risk of a fatty liver. Additionally, many women with polycystic ovary syndrome have elevated levels of insulin. By age 40, about 10 percent of overweight women with polycystic ovary syndrome develop abnormally high blood sugar levels (type 2 diabetes), and up to 35 percent develop prediabetes. Women with polycystic ovary syndrome are also at increased risk for developing metabolic syndrome, which is a group of conditions that include hypertension, increased belly fat, high levels of unhealthy fats and low levels of healthy fats in the blood, and high blood sugar levels. About 20 percent of affected adults experience sleep apnoea. Women with polycystic ovary syndrome are more likely to have mood disorders such as depression compared to the general population. (Genetics Home Reference, US National Library of Medicine, 2018)

Works Cited

1. Minerva Pediatrica. (2010). Polycystic ovary syndrome: a new pediatric disease? Minerva Pediatrica, 62(1), 85-92.
2. Sirmans, S. M., & Pate, K. A. (2014). Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology, 6, 1-13. doi:10.2147/CLEP.S37559
3. National Center for Biotechnology Information. (2016). Polycystic ovary syndrome. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK279054/
4. Farquhar, C. (2007). Ectopic pregnancy. Lancet, 370(9600), 1715-1722. doi:10.1016/S0140-6736(07)61687-8
5. Balen, A. H. (1995). Hypersecretion of luteinising hormone and ovarian steroids in women with recurrent miscarriage. BJOG: An International Journal of Obstetrics & Gynaecology, 102(4), 338-341. doi:10.1111/j.1471-0528.1995.tb10976.x
6. Hart, R. (2007). Polycystic ovary syndrome—prognosis and outcomes. Best Practice & Research Clinical Obstetrics & Gynaecology, 21(2), 289-299. doi:10.1016/j.bpobgyn.2006.12.002
7. J Clin Endocrinol Metab. (2004). Evidence-based guideline for the assessment and management of polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 89(8), 4898-4910. doi:10.1210/jc.2003-032047
8. March, W. A., Moore, V. M., Willson, K. J., Phillips, D. I., Norman, R. J., & Davies, M. J. (2010-2012). The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human Reproduction, 25(2), 544-551. doi:10.1093/humrep/dep399
9. Franks, S., McCarthy, M., & Hardy, K. (1997). Development of polycystic ovary syndrome: involvement of genetic and environmental factors. International Journal of Andrology, 20(5), 246-249. doi:10.1111/j.1365-2605.1997.tb00949.x
10. Diamanti-Kandarakis, E., Piperi, C., Patsouris, E., Korkolopoulou, P., Panidis, D., & Pawelczyk, L. (2012). Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochemistry and Cell Biology, 137(5), 633-644. doi:10.1007/s00418-012-0913-6