2. Polycystic Ovarian Syndrome
⢠PCOS is a common endocrinopathy affecting 4-12% of women of reproductive age.
⢠PCOS is characterized by oligo/anovulation, clinical and/or biochemical evidence of androgen excess,
obesity, insulin resistance and polycystic ovaries.
⢠It is associated with a number of comorbidities including:
ď Infertility
ďIncreased risk of T2DM and CVD
ďPsychological burden
ďRisk of endometrial cancer
1. Khademi A, Alleyassin A, Aghahosseini M, Tabatabaeefar L, Amini M. The Effect of Exercise in PCOS Women Who Exercise Regularly. Asian J Sports Med. 2010 Mar;1(1):35â40.
2. Harwood K, Vuguin P, DiMartino-Nardi J. Current Approaches to the Diagnosis and Treatment of Polycystic Ovarian Syndrome in Youth. HRP. 2007;68(5):209â17.
3. Lathief S, Pal L. Advances in Treatment Options for Polycystic Ovary Syndrome. Journal - Advances in Treatment Options for Polycystic Ovary Syndrome [Internet]. 2012 May 14.
3. Prevalence
⢠According to WHO estimates PCOS has affected 116 million women (3.4%) worldwide in 2012.
⢠Globally PCOS prevalence rate ranges from 2.2% to as high as 26%.
⢠In India, experts have claimed 10% of the women to be affected by PCOS.
⢠When PCOS is considered on the basis of menstrual disorder, PCOS is prevalent in:
ď30% - 40% of patients with primary or secondary amenorrhea.
ď80% of patients with oligomenorrhea.
1. Bharathi RV, Swetha S, Neerajaa J, Madhavica JV, Janani DM, Rekha SN, Ramya S, Usha B. An epidemiological survey: Effect of predisposing factors for PCOS in Indian urban and rural
population. Middle East Fertility Society Journal. 2017 Dec 1;22(4):313-6.
2. Barbosa G, SĂĄ LBPC de, Rocha DRTW, Arbex AK. Polycystic Ovary Syndrome (PCOS) and Fertility. Open Journal of Endocrine and Metabolic Diseases. 2016 Jan 12;06:58.
4. Study
⢠Cross-sectional survey
Participants
⢠1068 girls
⢠502 from urban and 572 from rural population
Result
⢠Prevalence rate of PCOS in India- 6% (based on self-answered questionnaire)
⢠Incident rate- 8.9% in urban areas, 1% in rural area
⢠In urban areas- 90.24% girls are aware, in rural areas â 8.34% are aware
⢠Family history has a strong association
A study conducted by Bharathi et.al (2017):
Bharathi RV, Swetha S, Neerajaa J, Madhavica JV, Janani DM, Rekha SN, Ramya S, Usha B. An epidemiological survey: Effect of predisposing factors for PCOS in Indian urban and rural
population. Middle East Fertility Society Journal. 2017 Dec 1;22(4):313-6.
5. Diagnostic Criteria
NIH/NICHD 1992
⢠Includes all of the
following:
⢠Clinical and/or
biochemical
hyperandrogenism
⢠Menstrual dysfunction
ESHRE/ASRM
(Rotterdam
criteria) 2004
⢠Includes two of the
⢠following:
⢠Clinical and/or
biochemical
hyperandrogenism
⢠Oligo-ovulation or
anovulation
⢠Polycystic ovaries
Androgen Excess
Society 2006
⢠Includes all of the
Following:
⢠Clinical and/or biochemical
hyperandrogenism
⢠Ovarian dysfunction
and/or polycystic ovaries
Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013 Dec 18;6:1â13.
6. Prevalence of PCOS using different
diagnostic criteria
Population NIH/NICHD
criteria
ESHRE/ASRM
(Rotterdam) criteria
Androgen excess
and PCOS society
criteria
Source
929 Iranian women 7.1% 14.6% 11.7% Tehrani et al
820 Iranian women 7% 15.2% 7.92% Mehrabian et al
728 Australian women 8.7% 17.8% 12% March et al
392 Turkish women 6.1% 19.9% 15.3% Yildiz et al
Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013 Dec 18;6:1â13.
7. Obesity â a significant risk factor in PCOS
Public Health England. âHealth Matters: Reproductive Health and Pregnancy Planningâ. GOV.UK. Accessed 6 October 2020. https://www.gov.uk/government/publications/health-
matters-reproductive-health-and-pregnancy-planning/health-matters-reproductive-health-and-pregnancy-planning.
50% of PCOS women are overweight or obese.
9. Insulin resistance and Impaired glucose
tolerance in PCOS
Insulin Action in PCOS: Relation with Obesity
⢠Prevalence of insulin resistance ranges from 50%â70%.
⢠Hyperinsulinemia produces a hyperandrogenic state by acting as a co-gonadotropin with luteinizing
hormone (LH), increasing androgen production and by reducing hepatic production of sex hormone
binding globulin.
⢠Women with PCOS are insulin resistant at the level of muscle, adipose tissue and liver.
1. Sam S. Obesity and Polycystic Ovary Syndrome. Obes Manag. 2007 Apr;3(2):69â73.
2. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013 Dec 18;6:1â13.
10. Glucose Tolerance in PCOS: Relation with Obesity
⢠PCOS is associated with high rates of glucose intolerance resulting from defects in insulin
action and β-cell function.
⢠Obese reproductive-age women with PCOS are at very high risk of glucose intolerance.
Sam S. Obesity and Polycystic Ovary Syndrome. Obes Manag. 2007 Apr;3(2):69â73.
Study
â˘Prospective, controlled study
Participants
â˘254 reproductive-age women with PCOS
â˘80 control women of comparable ethnicity, age and weight
Result
â˘Prevalence of glucose intolerance in women with PCOS (~40% combined IGT and
T2D) was much higher than control women (14% with IGT and 0% with T2D)
Study conducted by Legro et.al.
11. Clinical Management Strategies
Treatment for PCOS includes
⢠insulin-lowering drugs
⢠anti-androgen therapy
⢠oral contraceptives
⢠implementation of lifestyle changes, including weight loss if required.
Since PCOS is associated with multiple comorbidities, its treatment options differ
accordingly.
1. Lathief S, Pal L. Advances in Treatment Options for Polycystic Ovary Syndrome. Journal - Advances in Treatment Options for Polycystic Ovary Syndrome [Internet]. 2012 May 14 [cited 2019 Mar 4
2. Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril. 2006 Mar;85(3):679â88.
12. Treatment Options for Targeting Common Symptoms
Lathief S, Pal L. Advances in Treatment Options for Polycystic Ovary Syndrome. Journal - Advances in Treatment Options for Polycystic Ovary Syndrome [Internet]. 2012 May 14 [cited 2019 Mar 4];
⢠First-line treatment in PCOS management
⢠Suppresses LH, thereby reducing the stimulant effect of LH on androgen production
⢠Increases SHBG
⢠Offers protection against proliferative endometrial pathologies
ďCombined
Oral
Contraceptives
⢠Efficacious in mitigating the risk of endometrial pathologies in oligomenorrheic
women
ďProgesterone-
only Approach
13. Treatment Options for Managing Infertility in patients with PCOS
1. Lathief S, Pal L. Advances in Treatment Options for Polycystic Ovary Syndrome. Journal - Advances in Treatment Options for Polycystic Ovary Syndrome [Internet]. 2012 May 14 [cited 2019 Mar 4];
⢠Clomiphene Citrate (CC)
⢠Tamoxifen
Selective Estrogen
Receptor Modulators
(SERMs)
⢠Letrozole and Anastrozole are successfully used
⢠Leads to ovulation induction in CC-resistant patients
Aromatase Inhibitors
(AIs)
⢠In patients who fail to achieve success with SERMs and AIs
⢠Treatment protocol includes, lower dose step-up, low dose step-
down and combination of CC and low-dose gonadotropin
Gonadotropins
14. Treatment Options for Managing Infertility
Lathief S, Pal L. Advances in Treatment Options for Polycystic Ovary Syndrome. Journal - Advances in Treatment Options for Polycystic Ovary Syndrome [Internet]. 2012 May 14 [cited 2019 Mar 4];
⢠PCOS patients who fail to respond to SERMs and AIs, bilateral
electrocautery of the ovarian surface is the approach for
restoring ovulation.
⢠Spontaneous pregnancy rates increase following LOD.
Laparoscopic
Ovarian Drilling
(LOD)
â˘Spironolactone- Improved menstrual cyclicity and resumption of ovulation
at a dose of 50-200 mg/day.
â˘Finasteride- Blocks the conversion of testosterone to its more potent form
dihydrotestosterone (DHT) at a dose of 1-5 mg/day.
â˘Cyproterone Acetate- Efficacious in treating hirsutism at a dose of 2 mg.
Antiandrogens
15. A small to moderate weight loss of
about 5â10%
⢠Significantly improve IR,
⢠restore ovulation and improve
menstrual regularity and
conception
⢠ameliorate hyperandrogenism,
hirsutism and dyslipidemia.
PHYSICAL ACTIVITY
Lifestyle Interventions
DIET & NUTRITION
17. Calorie Restriction
Papavasiliou K, Papakonstantinou E. Nutritional support and dietary interventions for women with polycystic ovary syndrome. Nutrition and Dietary Supplements. 2017;9:63-85
PCOS patients are not always markedly overweight but PCOS is strongly associated with abdominal
obesity and insulin resistance.
Obese PCOS
Negative energy balance (with a deficit of 350â1000
kcal/day) seems to be the key factor leading to successful
body weight and fat loss and amelioration of menstrual
cycle and insulin sensitivity, irrespectively of the adopted
dietary pattern
Calorie Restriction: Weight Management & Body Composition
Dietary Modification &
Healthy Diet
18. Foods that contribute to Obesity
⢠Ultra-processed products tend to be energy-dense and high in
saturated and trans fat, added sugar, sodium, refined carbohydrates
⢠Consumption of these products may promote excess energy intake
because of their high energy density, as regulation of food intake
controls volume consumed rather than calories consumed
To achieve calorie deficit, one needs to avoid foods rich in the
following as these are high in calories and have been shown to
contribute to obesity
1. Sugar
2. Fat â Saturated and Trans
3. Sodium/Salt
4. Refined carbohydrates
Poti JM, Braga B, Qin B. Ultra-processed food intake and obesity: what really matters for healthâprocessing or nutrient content?. Current obesity reports. 2017 Dec 1;6(4):420-31.
19. Sugar is a big culprit in causing obesity and other
metabolic consequences in Indians
Rippe JM, Angelopoulos TJ. Relationship between added sugars consumption and chronic disease risk factors:
Current understanding. Nutrients. 2016 Nov;8(11):697.
21. FSSAI â EAT RIGHT
MOVEMENT
WHO RECOMENDATION
FSSAI AND WHO recommend reducing intake of
sugar in diet
Thus, watching out Sugar intake and selecting foods with Low or No Added
Sugars is important
22. Macro and Micronutrients in
PCOS
American Diabetes Association. Standards of medical care in diabetes -- 2009. Diabetes Care. 2009 Jan;32 Suppl 1:S13-61.
23. Distribution of macronutrients
American Diabetes Association. Nutrition principles and recommendations in diabetes. Diabetes care. 2004 Jan 1;27(suppl 1):s36-..
â¤
15â20%
24. Carbohydrates, Low GI and
High Fibre
Dietary
Carbohydrates
⢠Reduced carbohydrates diet results in:
⢠Lower measure of cell responsiveness and circulating insulin.
⢠Improvement in LDL cholesterol particle size, LDL concentration, and post prandial blood lipid
profile.
Glycemic
Index (GI)
⢠Food with low GI improves-
⢠Glucose control in PCOS and diabetes.
⢠Insulin sensitivity and menstrual regularity.
Dietary Fibre
⢠Food with high fibre -
⢠Contributes to satiety and weight management
⢠Helps combat insulin resistance
Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
25. 6 RCTs; 202
participants
Lost a mean of 1 kg
more
Body mass, total fat
mass, and body mass
index decreased
significantly
Lipid profile also
improved
Intervention: 5
weeksâ6 months
Thomas D, et al. Cochrane Database of Systematic Reviews. 2007; Issue 3, Art. No.: CD005105.
RCTs: Randomized controlled trials.
Impact of low glycemic index
or glycemic load diets in
overweight or obese people.
Low Glycemic Index and Load
Augment Weight Loss
26. 1. Barr S, et al. J Acad Nutr Diet. 2013;113(11):1523â1531. 2. Marsh KA, et al. Am J Clin Nutr. 2010;92:83â92. 3. Sordia-HernĂĄndez LH, et al. Clin Exp Obstet Gynecol.
2016;43(4):555â559.
PCOS: Polycystic ovary syndrome.
Benefits of Low Glycemic Index for
Insulin Sensitivity in PCOS
% Change in insulin resistance and
insulin sensitivity
Low glycemic index
helps reduce insulin
resistance and
improves insulin
sensitivity among
women with PCOS.1,2
27. Dietary
Proteins
⢠Proteins consumed at breakfast as compared with
lunch and dinner are more beneficial.
⢠Diet should deliver 20-25% of its calories as
protein.
⢠It helps the patient to lose weight or improve
glucose tolerance.
Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
Role of protein in PCOS
28. 1. Paddon-Jones D, et al. AJCN. 2008;87(5):1558Sâ1561S. 2. Westerterp KR. Nutr Metab (Lond). 2004;1(1):5. 3. Longland TM, et al. AJCN. 2016;103(3):738â746.
Protein and satiety:1,2
⢠Increases satiety to a greater extent
than carbohydrate or fat
⢠Facilitates a reduction in energy
consumption
Protein and weight loss/maintenance:1,3
⢠Increases total weight loss
⢠Increases the percentage of fat loss
⢠Promotes the maintenance or accretion
of fat-free mass
⢠Favors the retention of lean muscle
mass improving metabolic profile.
⢠Increases thermogenesisâaugments
energy expenditure
29. ⢠2-month, free-living,
randomized, single-blinded
study
⢠33 patients with PCOS
⢠Intervention: first the daily
energy intake was reduced
by 700 kcal; then a 240-
kcal supplement
containing either whey
protein or simple sugars
was added.
Kasim-Karakas SE, et al. ASRM. 2009;92(1):262â270.
PCOS: Polycystic ovarian syndrome; HDL-c: High-density lipoprotein cholesterol.
Protein Supplementation Enhances
Weight Loss in PCOS
30. Mehrabani HH, et al. J Am Coll Nutr. 2012;31(2):117â125.
PCOS: Polycystic ovary syndrome.
Benefits of the hypocaloric diet with high-protein, low glycemic-load diet
Reduced body weight
Decrease in high-sensitivity C-reactive protein
and androgen levels
Increase in insulin sensitivity
Dietary intervention
Conventional hypocaloric diet (15% of daily energy from protein)
Modified hypocaloric diet with a high-protein, low-glycemic load (30% of
daily energy from protein)
Investigated the effects of a high-protein, low glycemic-load diet compared with a conventional hypocaloric diet in obese
women with PCOS
RCT 60 overweight and obese women with PCOS 12 weeks
Benefits of High Protein, Low Glycemic
Index in PCOS
31. Te Morenga L, et al. Nutrients. 2017;9(12):1291.
Standard diet: low fat, relatively high
carbohydrate
Relatively high protein (up to 30% of
energy), relatively high fiber (>30 g/day)
diet
89 overweight or obese women 10 weeks
Results: 19% reduction in insulin sensitivity in the intervention
group when compared to the group consuming the standard diet
Randomized controlled trial
Effect of Moderately High Protein and
Fiber on Insulin Sensitivity
32. Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
Dietary fats
⢠Diet rich in mono saturated fatty acids decreases obesity and insulin resistance.
⢠Taken no more than 30% of the calorie content of the diet.
Antioxidants
⢠PCOS is associated with decreased antioxidant concentrations and it is
considered an oxidative state.
⢠Diet rich in fruits and vegetables, weight reduction, physical exercise, cessation
of smoking & alcohol consumption and an adequate number of sleeping hours to
be adopted to reduce oxidative stress.
Vitamin D
⢠Hypovitaminosis D is found in 80% of PCOS women.
⢠Supplementation of vitamin D (50,000 IU/week) restores normal menstrual
regularity and improves hyperandrogenism symptoms.
Role of other nutrients in PCOS
33. Role of nutrient supplementation in PCOS
Adapted from Gunalan et al
34. Inositol supplementation
Roles in:
⢠Insulin
sensitivity
⢠Lipid synthesis
⢠Oocyte
formation
⢠Oogenesis
Source Subjects Treatment Outcomes
Gerli et al 92 females with
polycystic ovaries
and oligomenorrhea
400 mcg folic acid intake in
placebo group (n=47) and
400 mcg folic acid + 4g
inositol in treatment group
(n=45), for 12-16 weeks
⢠Higher ovulation rate
⢠Weight loss
⢠Folicular maturation
⢠Circulating HDL
increases
Papaleo et
al
25 females with
PCOS and
oligo/amenorrhea
since childbearing
age
Myo-inositol + folic acid
(inofolic) (2g twice a day),
for 6 months
⢠Improved menstrual
cycle
⢠Healthy ovarian activity
⢠Serum free testosterone
reduces
Recommended dosage : 2-4 g per day
GĂźnalan E, Yaba A, YÄąlmaz B. The effect of nutrient supplementation in the management of polycystic ovary syndrome-associated metabolic dysfunctions: A critical review. J Turk Ger Gynecol Assoc. 2018
35. Omega-3 supplementation
⢠Reduce oxidative stress
⢠Decrease hypertension
⢠Improve lipid profile and anti-inflammatory activity
⢠Regulation of abnormal gene expression in PCOS
Source Subjects Treatment Outcomes
Mohammadi and
Rafraf
64 PCOS women;
20-35 years old
Treatment group (n=32)
received 4g/day omega-3
fatty acid; while placebo
group (n= 32) didnât.
Decreased CV risk:
⢠Serum paraoxonase I activity
improves
⢠Improved lipid profile
Oner and
Muderris
45 non-obese
PCOS patients
1500 mg/d omega-3
supplements for 6 months
⢠HOMA-IR and insulin level
reduces
⢠LH and testosterone reduces
⢠SHBG and TNF-ι increases
Recommended dosage : 1-4g/day
GĂźnalan E, Yaba A, YÄąlmaz B. The effect of nutrient supplementation in the management of polycystic ovary syndrome-associated metabolic dysfunctions: A critical review. J Turk Ger Gynecol Assoc. 2018
15;19(4):220â32.
36. Overall Tips on Modification of Diet and
Eating Pattern
⢠Intake of carbohydrates should count for 50%-55% of the
total energy.
⢠Diet high in fiber is beneficial.
⢠Higher protein i.e. 15-25% of daily energy, improves
satiety and insulin sensitivity.
⢠Eating not more than 30% of daily calories as fat. Avoiding
red meat.
⢠Consuming at least five portions of fruit or vegetables per
day.
Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
37. Overall Tips on Modification of Diet and Eating
Pattern
⢠Regularly eating and focusing on food intake of three to four meals
per day.
⢠Not skipping breakfast.
⢠Calorie intake should be distributed between several meals per day
with low intake from snacks and drinks.
⢠Avoid foods rich in fats and Sugars
Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
Address Emotional eating and sugar cravings
38. Exercise and Physical Activity
⢠Exercise improves menstrual abnormalities and restores ovulation in obese patients
with PCOS
⢠According to Thomson et al., 2008, exercise exerts its beneficial effects on body
composition with a 45% greater reduction in fat-free mass.
⢠Moderate exercise for âĽ30 min per preference is essential
1. Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
2. Norman RJ, Davies MJ, Lord J, Moran LJ. The role of lifestyle modification in polycystic ovary syndrome. Trends in Endocrinology & Metabolism. 2002 Aug 1;13(6):251â7.
39. Other Lifestyle modification for the management of PCOS
ďźReduction of psychosocial stress.
ďźCessation of smoking.
ďźModerate alcohol & caffeine consumption.
ďźGroup interaction/intervention to provide support in
implementing changes.
1. Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
2. Norman RJ, Davies MJ, Lord J, Moran LJ. The role of lifestyle modification in polycystic ovary syndrome. Trends in Endocrinology & Metabolism. 2002 Aug 1;13(6):251â7.
40. Key Takeaways
PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian
dysfunction in the absence of other specific diagnoses.
The diagnosis of PCOS requires careful application of well-standardized diagnostic methods.
In India, studies have shown 10% of the women to be affected by PCOS, with increasing incidence
PCOS results from a vicious circle of androgen excess favoring abdominal adipose tissue deposition
and visceral adiposity by inducing insulin resistance and compensatory hyperinsulinism.
Obesity leads to Insulin resistance and hyperinsulinemia are the major pathophysiological
mechanisms underlying PCOS.
41. Key Takeaways
Targets for the pharmacological treatment of PCOS might include androgen excess, oligo-ovulation
and insulin resistance, but lifestyle counselling should be provided in all cases to prevent or treat
obesity.
Healthy diet and Lifestyle intervention improves body composition, hyperandrogenism and insulin
resistance.
Consumption of adequate protein, high protein and low GI foods helps in weight management
Reducing intake of sugar and fat rich foods can contribute to reduction in incidence of obesity
Moderate exercise, reduction of smoking & psychosocial stressors, and dietary modification are the
lifestyle modification principles that would probably be of great benefit.
42. References
1. Khademi A, Alleyassin A, Aghahosseini M, Tabatabaeefar L, Amini M. The Effect of Exercise in PCOS Women Who Exercise Regularly. Asian J Sports Med.
2010 Mar;1(1):35â40.
2. Harwood K, Vuguin P, DiMartino- Nardi J. Current Approaches to the Diagnosis and Treatment of Polycystic Ovarian Syndrome in Youth. HRP.
2007;68(5):209â17.
3. Lathief S, Pal L. Advances in Treatment Options for Polycystic Ovary Syndrome. Journal - Advances in Treatment Options for Polycystic Ovary Syndrome
[Internet]. 2012 May 14 [cited 2019 Mar 4].
4. Bharathi RV, Swetha S, Neerajaa J, Madhavica JV, Janani DM, Rekha SN, Ramya S, Usha B. An epidemiological survey: Effect of predisposing factors for
PCOS in Indian urban and rural population. Middle East Fertility Society Journal. 2017 Dec 1;22(4):313-6.
5. Barbosa G, SĂĄ LBPC de, Rocha DRTW, Arbex AK. Polycystic Ovary Syndrome (PCOS) and Fertility. Open Journal of Endocrine and Metabolic Diseases.
2016 Jan 12;06:58.
6. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013 Dec 18;6:1â13.
7. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. International Journal of Obesity. 2002
Jul;26(7):883â96.
8. Escobar- Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nature Reviews Endocrinology. 2018 May;14(5):270â
84
9. Sam S. Obesity and Polycystic Ovary Syndrome. Obes Manag. 2007 Apr;3(2):69â73.
10. Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril. 2006
Mar;85(3):679â88
11. Paliwal M, et.al. Diet and Nutrition Management in Polycystic Ovary Syndrome. IJFANS. July 2016, Vol. 5, No. 3.
12. Norman RJ, Davies MJ, Lord J, Moran LJ. The role of lifestyle modification in polycystic ovary syndrome. Trends in Endocrinology & Metabolism. 2002
Aug 1;13(6):251â7
13. GĂźnalan E, Yaba A, YÄąlmaz B. The effect of nutrient supplementation in the management of polycystic ovary syndrome-associated metabolic
dysfunctions: A critical review. J Turk Ger Gynecol Assoc. 2018 15;19(4):220â32.
A randomized controlled intervention study by Mehrabani et al. investigated the effects of a high-protein, low glycemic-load diet compared with a conventional hypocaloric diet in obese women with PCOS. The authors found that both diets significantly led to reduced body weight and androgen levels. Compared to the conventional diet, the high-protein, low glycemic-load diet resulted in a significant increase in insulin sensitivity and a decrease in high-sensitivity C-reactive protein level.
Reference
Mehrabani HH, Salehpour S, Amiri Z, et al. Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in overweight and obese women with polycystic ovary syndrome: A randomized controlled intervention study. J Am Coll Nutr. 2012;31(2):117â125.
Polycystic ovarian syndrome is one of the most common endocrinopathies affecting 4-12% of women of reproductive age.
PCOS is a combination of disorders with oligo/anovulation, clinical and/or biochemical evidence of androgen excess, obesity, insulin resistance and polycystic ovaries on ultrasound.
It is a complex multigenetic disorder where disordered gonadotropin release, dysregulation of steroidogenesis, hyperinsulinism and insulin resistance play a role.
PCOS is additionally associated with a spectrum of comorbidities that include infertility, increased risk of type 2 diabetes and of cardiovascular disease (CVD), psychological burden, and risk of endometrial pathologies including endometrial cancer.
World Health Organization estimates that PCOS has affected 116 million women (3.4%) worldwide in 2012. Globally, PCOS prevalence rates are highly variable, ranging from 2.2% to as high as 26%.
In India, experts claimed 10% of the women to be affected by PCOS.
When PCOS is considered in the presence of menstrual disorder, diagnosis of PCOS is obtained in 30% - 40% of patients with primary or secondary amenorrhea and in 80% of patients with oligomenorrhea.
Bharathi RV et.al conducted a study, that established the prevalence rate of PCOS in India to be around 6% based on the self-answered questionnaire. It is also noticed that the incidence rate is higher (8.9%,) in urban area while 1% in the rural area.
From the survey, it was observed that 90.24% of girls knew about PCOS in urban and only 8.34% of the rural population were aware.
It was also estimated that family history has a strong association in incidence and manifestation of the disorder
Diagnostic criteria for PCOS have been offered by three groups:
The National Institutes of Health/National Institute of Child Health and Human Disease (NIH/NICHD)
The European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM)
The Androgen Excess and PCOS Society
The NIH/NICHD and the Androgen Excess Society require that patients have symptoms of hyperandrogenism such as hirsutism, or hyperandrogenemia.
Whereas, ESHRE/ASRM (Rotterdam) criteria allows for the diagnosis of PCOS with ovulatory dysfunction and the presence of polycystic ovaries.
This data shows the prevalence of PCOS globally using different diagnostic criteria. Tehrani et al showed that in a population of 929 Iranian women, according to NIH/NICDH criteria 7.1 % had PCOS, 14.6% according to Rotterdam criteria and 11.7% according to Androgen excess criteria. Similarly March et al conducted a study with 728 Australian women, out of which 7% , 15.2% and 7.92% had PCOS according to NIH, Rotterdam and Androgen excess criteria respectively.
PCOS results from a vicious circle of androgen excess favouring abdominal adipose tissue deposition and visceral adiposity by inducing insulin resistance and compensatory hyperinsulinism, which further facilitates androgen secretion by the ovaries and adrenal glands in women with PCOS.
The interplay between polycystic ovary syndrome (PCOS) and abdominal adiposity might be the result of a vicious circle (represented by the black arrows) of androgen excess favouring abdominal visceral adiposity, which facilitates androgen excess of ovarian and/or adrenal origin by the direct effects (grey arrow) of several autocrine, paracrine and endocrine mediators (downregulation of adiponectin and upregulation of tumor necrosis factor (TNF), ILâ6 and leptin) or indirectly by the induction of insulin resistance and hyperinsulinism.
Insulin resistance is a common finding in PCOS that is independent of obesity.
The prevalence of insulin resistance in PCOS ranges from 50%â70% and occurs independently of obesity.
The effect of obesity on insulin resistance is additive to that of PCOS.
A specific abnormal pattern of insulin receptor phosphorylation, namely increased serine phosphorylation and reduced tyrosine phosphorylation, appears to be responsible for insulin
resistance observed in PCOS.
Hyperinsulinemia produces a hyperandrogenic state by acting as a cogonadotropin with luteinizing hormone (LH), increasing androgen production by theca cells and by reducing hepatic production of sex hormone binding globulin, resulting in higher concentrations of free androgens.
Women with PCOS are characterized by the âinsulin paradoxâ, i.e. they are insulin resistant at the level of muscle, adipose tissue and liver.
PCOS is associated with high rates of glucose intolerance resulting from defects in insulin action and Ă-cell function.
Obesity substantially enhances these defects so obese reproductive-age women with PCOS are at very high rates of glucose intolerance.
In a study of 254 reproductive-age women with PCOS and 80 control women of comparable ethnicity, age, and weight, the prevalence of glucose intolerance in women with PCOS (~40% combined IGT and type 2 diabetes) was much higher than that reported in the control women from the same study (14% with IGT and 0% with type 2 diabetes).
Treatment for PCOS patients typically includes insulin-lowering drugs, anti-androgen therapy, oral contraceptives, and the implementation of lifestyle changes, including weight loss if necessary. Since PCOS is associated with multiple comorbidities, its treatment options differ accordingly.
Treatment Options for Managing Infertility
Selective Estrogen Receptor Modulators: Selective estrogen receptor modulators (SERMs) represent the prototype of drugs that are of proven efficacy in achieving ovulation induction
Clomiphene Citrate
Tamoxifen
Aromatase Inhibitors: Letrozole and anastrozole are the two AIs that have demonstrated success with achieving ovulation induction in CC-resistant patients. Ovulatory response and pregnancy rates associated with Ais are comparable to those seen with CC, but comparative data are sparse.
Gonadotropins: In patients who are resistant to, or fail to achieve success with, first- and second-line strategies such as SERMs and AIs, ovarian stimulation through exogenous gonadotropins is of proven efficacy in achieving ovulation and reproductive success, albeit at the risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Individualized modifications of
treatment protocolsâincluding lower dose step-up, low dose step-down and minimal stimulation combining CC and low-dose gonadotropin23â have demonstrated success in mitigating these treatment-related risks in women with PCOS undergoing infertility treatment with gonadotropins
Assisted Reproductive Technologies
Laparoscopic Electrocautery of the Ovaries and/or Laparoscopic Ovarian Drilling: For patients with PCOS who have failed to respond to attempts at ovulation induction with first- and second-line strategies such as SERMs and AIs, bilateral electrocautery of the ovarian surface offers a high likelihood of restoring ovulation. It and is proposed to underlie the resumption of ovarian follicular growth. Spontaneous pregnancy rates within the year following LEO/LOD are comparable to those achieved with gonadotropin use, but without the risk of multiple pregnancies.
Antiandrogens
Spironolactone: Improved menstrual cyclicity and resumption of ovulation may be seen in women treated with spironolactone at doses ranging from 50â200 mg/day. Its efficacy against acne is partly mediated through a reduction of sebum production.
Finasteride: A 5-alpha reductase II inhibitor that blocks the conversion of testosterone to its more potent form DHT, finasteride has shown promise in the management of PCOS-related hirsutism
At doses of 1â5 mg/day, the drug is well tolerated and relatively safe when used to manage symptoms of hyperandrogenism.
Cyproterone Acetate: Cyproterone acetate (CA) is a synthetic steroid that binds to the steroid receptors, exerting progestogenic, antiandrogenic, and weak glucocorticoid-like activity. In combination with ethinyl estradiol in COC formulations (not available in the US) this agent has demonstrated efficacy in treating hirsutism in women with PCOS. In COC A is used at a 2 mg dose.
Treatment Options for Managing Metabolic Abnormalities
1. Metformin: A safe and well tolerated drug that is of proven efficacy in the management and prevention of type 2 diabetes, metformin is one of the insulin-sensitizing drugs most commonly used in the management of PCOS. Its mechanism of action centralizes around a metabolic pathway through decrease in hepatic gluconeogenesis via activation of the AMP-kinase pathway.
Improved ovulation rates are observed in a variable proportion of women with PCOS treated with metformin. In patients with PCOS, metformin is typically prescribed at doses ranging
from 500 mg/day to 850 mg three times a day.52 Higher doses have been shown to be more efficacious in contributing to net weight loss, particularly in the obese and morbidly obese PCOS population.
2. Myoinositol: Inositol is a member of the vitamin B complex family; two of its steroisomers, D-chiro-inositol (DCI) and myo-inositol (MYO), have been
studied to determine whether they can improve insulin sensitivity and hence whether they are relevant in PCOS management. Limited data on the comparative efficacy of MYO and metformin suggest that MYO may be superior in improving ovulatory response and pregnancy rates in women with PCOS. At the recommended doses of 2â4 g per day.
Treatment Options for Targeting Common Symptoms includes:
Combined Oral Contraceptives (COCs)-
They are used as the first-line treatment in PCOS management, COCs offer menstrual regulation and endometrial protection.
Provide a suppression of pituitary luteinizing hormone (LH), thereby reducing the stimulant effect of LH on androgen production.
⢠It increases hepatic sex hormone binding globulin (SHBG).
⢠It also offers protection against proliferative endometrial pathologies that oligomenorrheic and insulin-resistant women are particularly at risk of.
Progesterone-only Approach is efficacious in mitigating the risk of endometrial pathologies in oligomenorrheic women.
Treatment Options for Managing Infertility
1. Selective estrogen receptor modulators (SERMs) represent the prototype of drugs that are of proven efficacy in achieving ovulation induction. Clomiphene Citrate and Tamoxifen are generally used.
2. Aromatase Inhibitors: Letrozole and anastrozole are the two AIs that have demonstrated success, achieving ovulation induction in CC-resistant patients.
3. Gonadotropins are used in patients who fail to achieve success with SERMs and AIs. Individualized modifications of treatment protocols includes lower dose step-up, low dose step-down and minimal stimulation combining CC and low-dose gonadotropin.
Laparoscopic Electrocautery of the Ovaries and/or Laparoscopic Ovarian Drilling is adopted for patients with PCOS who failed to respond to SERMs and AIs, bilateral electrocautery of the ovarian surface offers a high likelihood of restoring ovulation. Spontaneous pregnancy rates are increased following LOD.
Antiandrogens
Spironolactone improves menstrual cyclicity and resumption of ovulation may be seen in women treated with spironolactone at doses ranging from 50â200 mg/day.
Finasteride blocks the conversion of testosterone to its more potent form DHT, at a dose of 1â5 mg/day.
Cyproterone Acetate: binds to the steroid receptors, exerting progestogenic, antiandrogenic, and weak glucocorticoid-like activity. This agent has demonstrated efficacy in treating hirsutism in women with PCOS at a dose of 2 mg.
Studies have confirmed that modest weight loss in patients with PCOS improves glucose tolerance, cardiovascular risk profile and reproductive function.
In dietary management it is important to reduce total calories consumed to standard levels for age and activity.
A daily calories deficit of 200 kcal/day will prevent weight gain.
Short term meal replacement followed by dietary macronutrient restriction enhances weight loss in polycystic ovary syndrome.
Letâs discuss specifically for each type of diet-
Sugar consumption is one of the leading causes of Obesity in Indian scenario. It leads to several problems like weight gain, insulin resistance, obesity and so on further leading to metabolic disorders
hypothalamic-pituitary gonad (HPG)
Fundamentally, obesity influences fertility and male reproductive system through its negative impact on erectile dysfunction and semen parameters
When WHR was used to measure obesity instead of BMI, the similar tendency of negative correlation between obesity and sperm parameters was not found. So, the inconsistency may be due to measurement techniques
evidences abound that impaired spermatogenesis and altered sperm parameters such as decreased total sperm count and concentration are significantly connected to obese men. Undoubtedly, it can be a factor in subfertility or infertility of couples.
hypothalamic-pituitary gonad (HPG)
Fundamentally, obesity influences fertility and male reproductive system through its negative impact on erectile dysfunction and semen parameters
When WHR was used to measure obesity instead of BMI, the similar tendency of negative correlation between obesity and sperm parameters was not found. So, the inconsistency may be due to measurement techniques
evidences abound that impaired spermatogenesis and altered sperm parameters such as decreased total sperm count and concentration are significantly connected to obese men. Undoubtedly, it can be a factor in subfertility or infertility of couples.
According to a Cochrane review, overweight or obese people on low glycemic index (LGI) lost more weight and had more improvement in lipid profiles than those receiving comparison diets.
Body mass, total fat mass, body mass index, total cholesterol, and LDL-cholesterol all decreased significantly more in the LGI group.
In studies comparing ad libitum LGI diets to conventional restricted energy low-fat diets, participants fared as well or better on the LGI diet, even though they could eat as much as desired.
Thus, lowering the glycemic load of the diet appears to be an effective method of promoting weight loss and improving lipid profiles and can be simply incorporated into a person's lifestyle.
Reference
Thomas D, Elliott EJ, Baur L. Low glycaemic index or low glycaemic load diets for overweight and obesity. Cochrane Database of Systematic Reviews. 2007; Issue 3, Art. No.: CD005105.Â
Barr et al. determined the efficacy of an isocaloric low-glycemic index (LGI) dietary intervention on changes to insulin sensitivity in women with polycystic ovary syndrome (PCOS).2 A nonrandomized 12-week LGI dietary intervention, preceded by a 12-week habitual diet control phase and proceeded by a 12-week follow-up phase was conducted. The authors found the measures of insulin sensitivity improved after intervention (p=0.03).1 Similarly, in a study by Marsh et al., overweight and obese premenopausal women with PCOS were asked to consume either an ad libitum LGI diet or a macronutrient-matched healthy diet for 12 months or until they achieved a 7% weight loss. The study reported that the whole-body insulin sensitivity improved more with the LGI diet than with the conventional healthy diet.2
In women with PCOS, Sordia-HernĂĄndez et al. reported an improvement in the number of ovulatory cycles in those who consumed a low glycemic index diet. This could be secondary to an improvement in insulin resistance.3
References
Barr S, Reeves S, Sharp K, et al. An isocaloric low glycemic index diet improves insulin sensitivity in women with polycystic ovary syndrome. J Acad Nutr Diet. 2013;113(11):1523â1531.
Marsh KA, Steinbeck KS, Atkinson FS, et al. Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr. 2010;92:83â92.
Sordia-HernĂĄndez LH, Ancer RodrĂguez P, Saldivar Rodriguez D, et al. Effect of a low glycemic diet in patients with polycystic ovary syndrome and anovulationâa randomized controlled trial. Clin Exp Obstet Gynecol. 2016;43(4):555â559.
Protein intake influences satiety as well as weight loss and maintenance.
Satiety1,2
Protein generally increases satiety to a greater extent than carbohydrate or fat and may facilitate a reduction in energy consumption under ad libitum dietary conditions.
Weight loss and maintenance1,3
Several studies have suggested that high-protein diets may increase total weight loss and increase the percentage of fat loss. Protein intake also aids in the maintenance or accretion of fat-free massâin some individuals, a moderately high-protein diet may provide a stimulatory effect on muscle protein anabolism, favoring the retention of lean muscle mass while improving metabolic profile. Moreover, high-protein diets are associated with increased thermogenesis, which augments energy expenditure.
References
Paddon-Jones D, Westman E, Mattes RD, et al. Protein, weight management, and satiety. AJCN. 2008;87(5):1558Sâ1561S.
Westerterp KR. Diet induced thermogenesis. Nutr Metab (Lond). 2004;1(1):5.
Longland TM, Oikawa SY, Mitchell CJ, et al. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: A randomized trial. AJCN. 2016;103(3):738â746.
Dietary fats:
Diet rich in mono saturated fatty acids (MUFA), has been widely accepted as a gold standard for healthy diets. It decreases obesity and insulin resistance in patient with PCOS.
Dietary fat should account not more than 30% of the calorie content of the diet. The remainder of the fat content should be a balanced mixture of unsaturated fat including cooking oils and spreads.
Antioxidants: Polycystic ovary syndrome is associated with decreased antioxidant concentrations and it is considered an oxidative state. Therapeutic strategy to reduce the oxidative stress includes diet rich in fruits and vegetables, weight reduction, physical exercise, smoking cessation, alcohol consumption reduction and adequate number of sleeping hours.
Vitamin D: Hypovitaminosis D is found in 80% of PCOS women. Supplementation of vitamin D (50,000 IU/week) helps in restoring normal menstrual regularity and improving hyperandrogenism symptoms, weight loss and follicle maturation.
Nutrition-associated signalling pathways play a central role in the regulation of ovarian follicle growth and ovulation rates. Therefore, nutritional supplementation may contribute to overcome complications of PCOS such as immature oocyte, IR, hyperandrogenism, and oxidative stress. Various vitamin supplements like Vit B, D E play role in reducing elevated Hcy levels, insulin resistance and oxidative stress respectively. Vitamin-like nutrient supplements such as Carnitine reduces hyperandrogenism and hyperinsulinemia, while bioflavonoids reduces insulin resistance and oxidative stress. Mineral supplements like calcium, magnesium, zinc, selenium plays role in reducing insulin resistance, oxidative stress and hyperinsulinemia.
Inositol derived metabolites belong to family of vitamin B complex. They play essential roles in insulin sensitivity as second messengers, dyslipidemia, oocyte formation and oogenesis.
Various studies have reported the therapeutic role of inositol supplements in PCOS. In 1 of them 92 females with polycystic ovaries and oligomenorrhea participated. Out of them 45 were treated with 400 mcg folic acid + 4g inositol for 12-16 weeks, and the rest were placebo. The treated group had higher ovulation rate, weight loss, follicular maturation and higher circulating HDL.
Another study showed that 25 PCOS patients with oligo or amenorrhea since childbearing age received myo-inositol + folic acid for 6 months and had improved menstrual cycle, healthy ovarian activity and reduced serum free testosterone.
2-4 g/day is the dose recommended.
Omega 3 fatty acids are polyunsaturated fatty acids that reduce oxidative stress, decrease hypertension, improve lipid profile and anti-inflammatory activity. Recently, they have been considered for the treatment of PCOS, as their therapeutic mechanism regulate the abnormal gene expression.
A study with 64 20-35 years old PCOS patients showed decreased CV risk in the treatment group receiving 4g/day omega 3 supplement.
Similarly another study with 45 non-obese PCOS patients receiving 1500 mg/day omega-3 for 6 months showed reduced HOMA-IR, insulin levels. LH and testosterone and higher SHBG and TNF alpha.
The recommended dose is 1-4g/day
Following eating pattern should be adopted, like-
Intake of carbohydrates should count for 50%-55% of the diet initially.
Concentrating on low GI foods, those high in fiber.
Higher protein i.e. 25% of daily energy, content improves satiety and insulin sensitivity.
Eating not more than 30% of daily calories as fat
Avoiding red meat.
Consuming five portions of fruit or vegetables per day.
Eating regularly and focusing on food intake on three to four meals per day.
Not skipping breakfast.
It is a rational approach to lifestyle management in PCOS that will help the practitioner engage with the patient, and allow both practitioner and patient to manage this complex disorder in rational manner.
Following eating pattern should be adopted, like-
Intake of carbohydrates should count for 50%-55% of the diet initially.
Concentrating on low GI foods, those high in fiber.
Higher protein i.e. 25% of daily energy, content improves satiety and insulin sensitivity.
Eating not more than 30% of daily calories as fat
Avoiding red meat.
Consuming five portions of fruit or vegetables per day.
Eating regularly and focusing on food intake on three to four meals per day.
Not skipping breakfast.
It is a rational approach to lifestyle management in PCOS that will help the practitioner engage with the patient, and allow both practitioner and patient to manage this complex disorder in rational manner.
Several studies have suggested that exercise improves menstrual abnormalities and restores ovulation in obese patients with PCOS
Exercise exerts its beneficial effects on body composition with a 45% greater reduction in fat free mass as stated by Thomson et al., 2008.
Lifestyle modification suggested for treatment of polycystic ovary syndrome (PCOS) in overweight women:
Moderate exercise for âĽ30 min per day.
Modification in diet i.e. daily intake of fat â¤30%, â saturated and trans fat and glycemic load, â fiber and polyunsaturated fat.
Establishing an energy deficit of 500â1000 kcal dayâ1.
Reduction of psychosocial stress.
Cessation of smoking.
Moderate alcohol consumption.
Moderate caffeine consumption.
Group interaction/intervention to provide support and assisting in implementing changes.
A randomized controlled intervention study by Mehrabani et al. investigated the effects of a high-protein, low glycemic-load diet compared with a conventional hypocaloric diet in obese women with PCOS. The authors found that both diets significantly led to reduced body weight and androgen levels. Compared to the conventional diet, the high-protein, low glycemic-load diet resulted in a significant increase in insulin sensitivity and a decrease in high-sensitivity C-reactive protein level.
Reference
Mehrabani HH, Salehpour S, Amiri Z, et al. Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in overweight and obese women with polycystic ovary syndrome: A randomized controlled intervention study. J Am Coll Nutr. 2012;31(2):117â125.