Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by hyperandrogenism (which primarily manifests as hirsutism, acne, and, occasionally, virilization), oligo ovulation/anovulation, and/or the presence of polycystic ovaries. The diagnosis involves a complete history and physical examination to evaluate for ovulatory dysfunction and clinical signs of hyper androgenesis.
Laboratory tests are performed to confirm biochemical hyperandrogenism and exclude other conditions with a potentially similar clinical picture (e.g., congenital adrenal hyperplasia). Ultrasound may be performed in adults to identify cystic follicles and assess ovarian volume but is not required for diagnosis if ovulatory dysfunction and hyperandrogenism are present. Management consists of lifestyle modifications combined with specific treatment, which is tailored to the patient’s reproductive goals. In women who do not wish to conceive, combined oral contraceptive pills are indicated to regulate menses and treat hyperandrogenism.
For women who wish to conceive, the goal of treatment is to induce ovulation. Women with PCOS are twice as likely to develop metabolic syndrome, which is associated with obesity, insulin resistance, hypercholesterolemia, and an increased risk of endometrial cancer. Therefore, all patients should be screened for co morbidities and receive specific treatment for these when necessary.
Patho physiology
- The exact patho physiology is unknown → ↑ in peripheral estrogen Strong association with obesity synthesis from adipose tissue and ↓ in peripheral sensitivity to insulin, Reduced insulin sensitivity (peripheral insulin resistance) and the consequent hyper insulinemia result in: Epidermal hyperplasia and hyperpigmentation (acanthosis nigricans)
- ↑ Androgen production in ovarian theca interna cells → imbalance between androgen precursors and the resulting estrogen produced in granulosa cells
- ↑ LH secretion disrupts the LH/FSH balance → impaired follicle maturation with cyst formation due to lack of follicle rupture and anovulation/oligo ovulation → infertility
- ↑ Androgen precursor release and ↑ estrogen production in adipose tissue
- Inhibition of SHBG in the liver → ↑ free androgens and estrogens
- ↑ Unopposed estrogen (lack of progesterone) during anovulatory cycle → endometrial hyperplasia → ↑ risk of endometrial carcinoma
Clinical features
Onset of symptoms typically occurs during adolescence
Menstrual irregularities
- Primary or secondary amenorrhea
- Oligomenorrhea
- Menorrhagia
- Infertility or difficulties conceiving
- Insulin resistance and associated conditions
- Metabolic syndrome (especially obesity ) → ↑ risk of sleep apnea
- Nonalcoholic fatty liver disease
Skin conditions
- Hirsutism
- Androgenic alopecia
- Acne vulgaris
- Oily skin
- Acanthosis nigricans
Psychiatric conditions
- Depression
- Anxiety disorders
Voice change may occur in severe forms of PCOS. However, it typically suggests a different underlying cause of hyperandrogenism
Pathology
- Macroscopic appearance
Multiple, brown cysts arranged in a circular pattern in the subcapsular region of the ovary
Cysts are relatively small and of approximately the same size.
[Polycystic ovary syndrome (PCOS; Stein-Leventhal syndrome)]- Microscopic appearance
Ovarian hypertrophy with thick capsule Stromal hyperplasia and fibrosis
Multiple enlarged cystic follicles Hyperluteinized theca cells Decreased granulosa cell layer [Polycystic ovary syndrome (PCOS; Stein-Leventhal syndrome)]
Diagnostics Approach
Early diagnosis is essential, as PCOS is associated with many conditions, including metabolic dysfunction and impaired fertility. It also has a significant impact on a woman’s emotional well-being and quality of life. Suspect PCOS in women of reproductive age with features of hyperandrogenism and/or ovulatory dysfunction Use the Rotterdam criteria to establish the clinical diagnosis. Obtain an initial diagnostic workup to exclude pregnancy and endocrine disorders (e.g., thyroid dysfunction, hyperprolactinemia, nonclassical CAH).
Perform a detailed assessment to evaluate for co morbidities. Screen for metabolic disorders regardless of BMI
Rotterdam criteria
- PCOS is diagnosed in adults based on the presence of at least two of the following criteria, after other endocrinological conditions, e.g., thyroid disease, hyperprolactinemia, have been excluded.
- Oligo ovulation and/or anovulation Hyperandrogenism (based on clinical features or laboratory studies): Examine patients for signs of acne, alopecia, and hirsutism ; obtain laboratory studies as needed. Enlarged and/or polycystic ovary on ultrasound . Ovarian volume ≥ 10 mL AND/OR the presence of multiple cystic follicles measuring 2–9 mm (string-of-pearls appearance) in one or both ovaries
Laboratory studies
Confirm hyperandrogenism : Obtain in all women with clinical features of PCOS, even if features are minimal or unclear.
↑ Testosterone: Use the calculated free testosterone, calculated bioavailable testosterone , or free androgen index . Direct free testosterone has poor sensitivity. [10]
↑ Androstenedione and ↑ dehydroepiandrosterone sulfate: limited role in diagnosis of PCOS, but useful for ruling out other causes of hyperandrogenism
Rule out differential diagnoses: e.g., pregnancy , endocrine disorders
All patients
TSH
Prolactin
17-hydroxyprogesterone
Patients with amenorrhea
Serum or urine hCG
Serum LH , FSH
Features of hypercortisolism : Consider measuring cortisol in 24-hour urine, late-night salivary cortisol, or a dexamethasone suppression test
A clinical picture of hyperandrogenism fulfills a diagnostic criterion of PCOS, even if serum androgen levels are normal.
An elevated LH(with LH:FSH ratio> 2:1) is a characteristic finding in most patients with PCOS but not necessary for diagnosis.
Ultrasound
- Parameters: An experienced clinician should assess the ovarian volume and, when feasible, the
- number and volume of follicles.
- Modalities: Transvaginal (preferred; use if acceptable to patient): offers the best visualization of ovarian follicles
- Transabdominal: should focus on measuring ovarian volume
- Identification of cystic follicles is not mandatory to diagnose PCOS. Evaluate for comorbidities
- Patients with PCOS are at risk of serious comorbidities, even at a young age. It is important to screen for these at the first visit and at regular intervals.
- Metabolic screening and monitoring
- Measure weight, height, and waist circumference; calculate BMI Measure at baseline and repeat every 6–12 months. For patients with elevated BMI: Obtain a fasting lipid profile and screen for symptoms of obstructive sleep apnea.
- Check blood pressure: Obtain at baseline and then at least once a year; measure more frequently based on individual risk.Assess glycemic status : Obtain at baseline and repeat every 1–3 years, depending on individual risk.
- Mental health and quality of life: Screen for anxiety, depression, and psychosexual dysfunction.
- Women with PCOS are at least twice as likely to have metabolic syndrome as women without PCOS.
Women with PCOS are also at increased risk for endometrial cancer. Screening is not routinely recommended, but clinicians should maintain a high index of suspicion and conduct a transvaginal ultrasound and/or endometrial biopsy if there are suggestive features (e.g., thickened endometrium, abnormal vaginal bleeding). [10]
Treatment Approach
Recommendations for all patients
- Encourage exercise and healthy eating (e.g. caloric restriction), and consider behavioral strategies and modifications (e.g., setting goals, eating more slowly).
- Target BMI < 25 kg/m2 (can reduce estrogen production in the adipose tissue)
- Screen for comorbidities and provide specific treatment.
Tailor additional therapeutic interventions based on:
- Reproductive goals, Co morbidities, Individual risk factors
- Features associated with PCOS (e.g., obesity, hyperandrogenism, difficulties conceiving) can have a negative psychosocial impact. If symptoms of anxiety and/or depression are identified, further mental health assessment and a referral to a mental health professional should be offered to the patient.
Patients not planning to conceive:
- For patients who do not wish to conceive, the therapeutic goals are to control menstrual irregularities and hyperandrogenism, treat comorbidities, and improve quality of life. Combined oral contraceptives
- Indication: first-line treatment for hyperandrogenism and/or menstrual cycle abnormalities
- Additional benefits: ↓ Endometrial hyperplasia → ↓ risk of endometrial carcinoma
- ↓ Menstrual bleeding
- ↓ Acne
- Treatment of hirsutism
- Metformin : improves menstrual irregularities, metabolic outcomes, and weight (especially when combined with lifestyle modifications Second-line treatment for menstrual irregularity in patients unable to take or tolerate COCs May be added to COCs and lifestyle modification to improve metabolic outcomes
- Antiandrogens : controversial role Examples: spironolactone , finasteride , flutamide Indications: can be considered for treatment of hirsutism and androgen -related alopecia in patients unable to take or tolerate COCs Additional recommendation: When using antiandrogens as an alternative to COCs , it is advisable to use other forms of contraception.
- Additional interventions: Other measures, like antiobesity medications or bariatric surgery , may be considered on a case-by-case basis.
- Patients planning to conceive
- The goals of treatment for patients who wish to conceive are management of comorbidities (e.g., weight loss for overweight or obese patients) and induction of ovulation
- Letrozole : first-line therapy for ovulation induction
- Improves pregnancy and live birth rates in patients with anovulatory infertility with no other causes Mechanism of action: aromatase inhibition reduces estrogen production, stimulating FSH secretion and inducing ovulation
- Clomiphene: alternative to letrozole May be preferred over metformin monotherapy in obese women with anovulatory infertilit Mechanism of action: inhibits hypothalamic estrogen receptors → disruption of the negative feedback mechanism governing estrogen production → ↑ pulsatile secretion of GnRH → ↑ FSH and LH → stimulation of ovulation
- Exogenous gonadotropin : The low-dose regimen is the second-line treatment for ovulation induction.
- Agents: exogenous FSH and human menopausal gonadotropin
- Indication: typically used if first-line therapies are unsuccessful; occasionally used as first-line if the drug and monitoring requirements are accessible
- Metformin Can be used as second-line monotherapy for fertility treatment. Combination with clomiphene may increase pregnancy rates, especially in obese women.
- First-line therapy for insulin resistance
- Additional fertility interventions
- Laparoscopic ovarian
- This hormonal shift can induce FSH secretion and improve ovarian function in patients with polycystic ovary syndrome.
- Second-line treatment for ovulation induction
- In vitro fertilization : can be offered as third-line therapy
- Bariatric surgery : no evidence of benefit in the treatment of infertility
Complications
Cardiovascular disease
Type 2 diabetes mellitus
Malignancy
(increased risk before menopause ) [13]
Endometrial cancer
Ovarian cancer
Pancreatic cancer
Kidney cancer
Endocrine cancers (except thyroid
Pregnancy loss
HOMOEOPATHIC APPROACH:
Amenorrhea :- Acon., All-c., Am-c., Anac., Anag., Apis, Apoc., Ars., Aur., # Aur-m., Bar-c., Bell., Benz-ac., Bry., Calc., Card-m., Caul., Caust., Cham., Chel., Chen-v., Chin., Cimic., Cina, Coca, Cocc., Colch., Coll., Coloc., Con., Cupr-a., CYCL., Dros., Dulc., Euphr., Ferr., Ferr-i., Gels., Goss., Graph., Guai., HAM., HELL., Helon., Hyos., Ictod., Ign., Iod., Kali-c., Kali-n., Kali-p., Lach., Lil-t., Mag-c., Mag-m., Mit., Nat-m., Nux-m., Nux-v., Ol-j., Ph-ac., Phos., Plat., Polyg., PULS., Rhus-t., Senec., SEP., Sil., Sin-a., Sin-n., Staph., Sulph., Thuj., Verat-v., Vib., Xan., Zinc.
Months :-
For several (ague) :- Puls.
Many :- Hell.
2 :- Senec.
Puberty, at :- Acon., Ant-c., Dig., Kali-c., SEP.
2 in (climaxis) :- Lach.
3rd, until :- Abies-n.
4 :- Sulph.
4 in (Bright’s disease) :- Ter.
5, of, standing :- Sulph.
6 :- Graph.
6, in chronic jaundice :- Iod.
Weeks, 6, constipation :- Glon.
Weeks, 6, restless at night :- Glon.
Weeks, 6, throbbing pains through temples and pressure and heaviness in head :- Glon.
Weeks, more than 10 :- Ther.
Ovaries :-
Ovaries, with anæmia of :- Ferr.
Ovarian atrophy, with anæmia :- Helon.
Ovarian irritation or disease, with :- Phyt.
Ovary, swelling of left :- Lach.
Scrofulous constitutions, in :- Sulph.
Scrofulous girls, especially of :- Bar-c.
Affections (undefined) :- Arn., Kreos., LYC., Pall., Plat.
Left, of :- Alumn., Arg-m., LACH., Lil-t., Lyc., Podo.
Left, in, worse at each menstrual nisus, distressing pain, burning when walking or riding, must lie down, pain extends through left iliac region into groin, and sometimes into left leg, pain sometimes burning :- Thuj.
Nervous disorders, with pronounced, especially in married women :- Syph.
Nervous disorders, of right :- Apis, Ars., Bell., Bry., Ferr., Glon., Lach., LYC., PALL., Podo.
Swelling and tenesmus, with, worse during menses :- Ham.
Enlarged (See Congested, Inflamed, Swelling, Tumor.) :- Aur-m-n., Carb-an., Kali-br., Spong., Ust.
Chronic, especially right :- Apis.
Tumors :- APIS, Apoc., Ars., Bar-m., Calc., Coloc., Iod., LYC., Plat., Podo.
Hard, right side :- Apis.
Left, in :- LACH.
Left 1st affected, tending to right :- Lach.
Soft, encysted :- Apis.
Tendency to :- Syph.
Urinary difficulties, with (cysts) :- Canth.
Sterility :- Anag., ¤ Aur-m., Bar-m., Bor., Brom., Calc., Cann-s., Canth., Ferr., Fil., Iod., Lach., Merc., Nat-c., NAT-M., Nat-p., Nux-m., Orig., Sep., Sil., Sulph., Teucr.
Frequent and early, ovum expelled at every menstrual period causing sterility :- Vib.
REFRENCES
- PCOS (Polycystic Ovary Syndrome) and Diabetes. https://www.cdc.gov/diabetes/basics/pcos.html. Updated: March 24, 2020. Accessed: April 30, 2020.
- American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology.. ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome.. Obstet Gynecol. 2018; 131 (6): p.e157-e171. doi: 10.1097/AOG.0000000000002656 . | Open in Read by QxMD
- Phiske M. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014; 5 (3): p.239. doi: 10.4103/2229-5178.137765 . | Open in Read by QxMD
- Strain G, Zumoff B, Rosner W, Pi-Sunyer X. The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss.. J Clin Endocrinol Metab. 1994; 79 (4): p.1173-6. doi: 10.1210/jcem.79.4.7962291 . | Open in Read by QxMD
- Hoeger KM, Dokras A, Piltonen T. Update on PCOS: Consequences, Challenges, and Guiding Treatment. The Journal of Clinical Endocrinology & Metabolism. 2020; 106 (3): p.e1071-e1083. doi: 10.1210/clinem/dgaa839 . | Open in Read by QxMD
- Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018; 110 (3): p.364-379. doi: 10.1016/j.fertnstert.2018.05.004 . | Open in Read by QxMD
- Williams T, Mortada R, Porter S. Diagnosis and Treatment of Polycystic Ovary Syndrome.. Am Fam Physician. 2016; 94 (2): p.106-13.
- Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013; 98 (12): p.4565-4592. doi: 10.1210/jc.2013-2350 . | Open in Read by QxMD
- International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018. https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS_Evidence-Based-Guidelines_20181009.pdf. Updated: February 1, 2018. Accessed: May 3, 2021.
- EBERSOLE AM, BONNY AE. Diagnosis and Treatment of Polycystic Ovary Syndrome in Adolescent Females. Clinical Obstetrics & Gynecology. 2020; 63 (3): p.544-552. doi: 10.1097/grf.0000000000000538 . | Open in Read by QxMD
- Screening and Management of the Hyperandrogenic Adolescent.
- Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews. 2018 . doi: 10.1002/14651858.cd010287.pub3 . | Open in Read by QxMD
- Yin W, Falconer H, Yin L, Xu L, Ye W. Association Between Polycystic Ovary Syndrome and Cancer Risk. JAMA Oncology. 2019; 5 (1): p.106. doi: 10.1001/jamaoncol.2018.5188 . | Open in Read by QxMD
Dr. Ashok Yadav (Head Of Department, Deprtment Of Practice Of Medicine), Dr Navneet Kaur Md(Pgr) Deprtment Of Practice Of Medicine, Dr. Garima Chaudhary Md(Pgr) Deprtment Of Practice Ofmedicine, Dr. Mansi Mishra Md(Pgr) Deprtment Of Practice Ofmedicine, Dr. Himani Shah Md(Pgr) Deprtment Of Practice Ofmedicine
