Polycystic Ovary Syndrome (PCOS)
Introduction and Facts
Polycystic Ovary Syndrome (PCOS), also known as hyperandrogenic anovulation (HA), is an endocrine system disorder that causes infertility in women of reproductive age. The etiology of this disease is not known with certainty. This disease includes oligogenic, which is influenced by genetic and environmental factors; the genetic factor involved is X-Linked dominant.
Pathophysiology
Women with PCOS have androgen and estrogen metabolism abnormalities, increasing testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). Hormonal imbalance in PCOS is also closely related to hyperinsulinemia, peripheral insulin resistance, and obesity. These features are associated with hypersecretion of luteinizing hormone (LH) and androgens with low or normal serum follicle-stimulating hormone (FSH) concentrations. LH, compared to FSH, interferes with the ovulation process because it causes incomplete follicular development resulting in polycystic ovarian morphology. Symptoms that often occur are long and infertile menstrual cycles. However, in some patients, there may be normal levels of androgen hormones.
Clinical Symptoms and Complications
The clinical manifestations of PCOS vary from mild menstrual disturbances to impaired reproductive and metabolic functions.
Diagnosis
PCOS women have a predisposition to type 2 diabetes mellitus or cardiovascular disorders. The National Institutes of Health (NIH) in 1990 established the criteria for the diagnosis of PCOS. The Rotterdam European Society for Human Reproduction/American Society of Reproductive Medicine (ASRM) revised the diagnostic criteria in 2003.
A diagnosis of PCOS must have 2 of 3 criteria. In 2006, the Androgen Excess Society (AES) suggested that the NICHD/NIHS criteria could be used with modifications, including the Rotterdam criteria.
The AES defines PCOS as a disorder primarily involving androgen excess, together with various combinations of phenotypic features (such as hyperandrogenemia, hirsutism, oligo-ovulation/anovulation, and/or polycystic ovaries) that can make a more accurate diagnosis.
a. NICHD/NIH (1990) criteria; Must have both criteria:
- Oligo-ovulation/chronic anovulation
- Hyperandrogenemia with the exclusion of other possibilities such as congenital adrenal hyperplasia and Cushing's syndrome.
b. Rotterdam ESHRE/ASRM criteria (2003); Must have 2 of 3 criteria:
- Hyperandrogenemia
- Oligo-ovulation/anovulation
- Polycystic ovaries from ultrasound results. More than 12 follicles 2-9 mm in diameter or increased ovarian volume >10 mL
c. Androgen Excess Society (AES) Criteria (2006); Must have both criteria:
- Oligo-ovulation/anovulation and/or polycystic ovaries from ultrasound.
- Clinical and/or laboratory features show an increase in androgen hormones
Management and Treatment
1. Lifestyle and Nutrition Changes:
Lifestyle changes are the main steps to regulate diet and exercise, considering obesity triggers insulin resistance and metabolic syndrome. Weight loss decreases circulating androgens and insulin, improves lipids, and increases FSH, reducing physical symptoms such as hirsutism, alopecia, acne, skin tags, normalizing the menstrual cycle, and stimulating ovulation.
2. Pharmacological Approach
- Anovulation.
Clomiphene citrate is still the main treatment option to stimulate ovulation in PCOS cases. The initial dose is 50 mg/day for five days from the 3rd day of menstruation. If ovulation occurs, but fertilization does not occur in the first cycle, the dose can still be continued at 50 mg/day in the next cycle. However, if the initial cycle does not occur ovulation, the dose can be increased to 100 mg/day in the next cycle. Increasing this dose also has the risk of triggering clomiphene resistance. Administration can be repeated up to 6 cycles.
- Antidiabetic drugs
Insulin resistance with hyperinsulinemia has an essential role in hyperandrogenemia and insulin resistance. Metformin significantly reduced body mass index (BMI) at a dose of >1500 mg/day, and long-term treatment duration also showed a sustained effect on weight loss >8 weeks.
- Aromatase Inhibitors
Aromatase inhibitors are commonly used as hormone-responsive breast cancer therapy, and have been studied to induce ovulation in PCOS; Functionally suppress estrogen production through stimulation of the hypothalamic-pituitary axis which has implications for increasing gonadotropin-releasing hormone (GnRH) and follicle stimulating hormone (FSH).
- Oral contraceptives
The regulation of birth control pills overcomes PCOS, especially in regulating the menstrual cycle. These medications also reduce hirsutism, acne, and androgen levels. The combination of estrogen and progestin is the primary oral contraceptive used to treat hirsutism and acne associated with PCOS.
- Other Category Drugs
Medroxyprogesterone acetate 5-10 mg/day for 10-14 days every month aims to treat dysfunctional uterine bleeding and amenorrhea in PCOS patients who are not planning to become pregnant.
3. Second-line therapy:
- Gonadotropins
Administration of exogenous gonadotropin hormones, namely a combination of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (HMG). The mechanism of action of gonadotropins is to stimulate ovulation and maximize follicular development.
- Laparoscopic Ovarian Surgery
Laparoscopic ovarian surgery is also considered second-line therapy but is an invasive method and requires general anesthesia.
4. Third-line Therapy:
In vitro fertilization (IVF). IVF is an option in case of failure of first and second line therapy. IVF is usually the choice for severe abnormalities in women (endometriosis, tubal obstruction, and other obstetric disorders that impair fertility) and men (azoospermia and male fertility disorders).
5. Alternative Medicine
Alternative treatment modalities include kinesiology, herbalism, homeopathy, reflexology, acupressure, acupuncture, ovulation induction, and massage therapy. Acupuncture is the most common modality and has been shown to regulate menstrual cycles in PCOS patients, lose weight, improve mood, and reduce headaches. The application of acupuncture needles can increase blood flow, stimulate organs, contribute to normalizing hormone levels, and improve reproductive system function.
Reference:
Ni Luh Putu Rustiari Dewi. Approach to therapy for polycystic ovary syndrome (PCOS). Mirror of the World of Medicine [Internet]. 2020 [cited 2021 Aug 27];290:47(9):703-5.
