Is polycystic ovary syndrome difficult to treat?

For women of childbearing age, they must learn to protect their ovaries. The reason why many women lose the opportunity to become mothers is that they do not receive enough attention after their ovaries become diseased, resulting in the disease becoming more and more serious and eventually losing their fertility. Such things are indeed sad, so I would like to remind all women to learn how to protect their ovaries and their health. So, is polycystic ovary syndrome difficult to treat?

1. Medication

Currently, drug treatment for PCOS has replaced surgical treatment as the first-line treatment method, and the purpose of treatment is mainly related to the patient's fertility requirements.

(1) Drug treatment to reduce hyperandrogenism

1) Oral contraceptive pills (OCPs) have been used as a traditional long-term treatment for women with PCOS, mainly to protect the endometrium, regulate the menstrual cycle, and improve hirsutism and/or acne by reducing androgen production in the ovaries. OCP can reduce hyperandrogenism in PCOS patients. Among them, the most commonly used OCP for reducing hyperandrogenemia is cyproterone acetate, which has progestin activity and can combine with ethinyl estradiol to exert an anti-androgenic effect. It can also bind to the dihydrotestosterone receptor in the cytoplasm of hair follicles, blocking the conduction of androgen effects to the cell nucleus. By inhibiting the activity of this receptor, it inhibits the activity of 5α-reductase, reduces DHT production and gonadotropin synthesis, and reduces gonadotropin levels, which reduces steroid synthesis, increases SHBG levels and reduces gonadotropin levels. Therefore, cyproterone acetate has been used as the first choice for the treatment of PCOS hirsutism in the past 20 years. Continuous treatment for more than 6 cycles is effective for 60% to 80% of hirsutism patients. OCP is a simple and economical treatment for PCOS patients who do not desire fertility. However, recent studies have shown that it may reduce insulin sensitivity and glucose tolerance in women with PCOS. Other common side effects include headache, weight gain, mood changes, decreased libido, gastrointestinal reactions and breast pain, which should be paid attention to.

2) Glucocorticoids

For the treatment of hyperandrogenism caused by excessive adrenal androgen synthesis, dexamethasone and prednisone are more effective because they have a greater affinity for receptors, inhibiting pituitary ACTH secretion and reducing ACTH-dependent adrenal androgen secretion. With long-term use, be aware of the possibility of hypothalamic-pituitary-adrenal axis suppression.

3) Spironolactone

It is an aldosterone analogue that has similar effectiveness in enzyme inhibition to cyproterone acetate, so the two treatments have similar effects. At the same time, it has an anti-androgen effect. Its mechanism of action for treating hyperandrogenism is to competitively bind to androgen receptors, and to competitively bind to receptors with dihydrotestosterone (DHT) in peripheral tissues, inhibiting 17α hydroxylase and reducing T and A.

4) Flutamide

It is a steroid complex with potent and highly specific non-steroidal antiandrogen properties. It has no intrinsic hormone or anti-gonadotropin effects and cannot reduce steroid synthesis, but it inhibits the androgen effect by receptor binding. Compared with cyproterone acetate, serum androgen levels (including total testosterone and free testosterone) increased after treatment, but because the androgen target organ effects were antagonized, clinical manifestations did not worsen despite the increase in serum androgen levels. Long-term and excessive use of the drug may cause liver damage. It is also unclear whether it will cause fetal malformations, so contraception should be used while taking the drug.

(2) Ovulation-inducing drug therapy

PCOS patients who want to have children often need ovulation induction treatment to become pregnant. The drug-induced ovulation treatment of PCOS has made great progress in the past 50 years, but some patients have poor efficacy with conventional methods. Therefore, choosing the right plan is the key to ovulation induction treatment.

1) Clomiphene (CC) In 1961, Greenblatt reported the use of clomiphene for ovulation induction treatment. CC has become the drug of choice for ovulation induction treatment of PCOS. CC can bind to the hypothalamic estrogen receptors, blocking the central nervous system's response to circulating estrogen levels, increasing the secretion of pulsatile GnRH and gonadotropin, and further causing follicle growth and development. In addition, CC can also directly affect the pituitary gland and ovary, respectively increasing the secretion of gonadotropin and synergistically enhancing FSH-induced aromatase activity. CC can also exhibit antiestrogenic properties in other parts of the female reproductive tract, particularly the endometrium and cervix (thickening cervical mucus). These anti-estrogenic effects can have a negative impact on pregnancy. Treatment often starts after the natural menstrual cycle or after the withdrawal of progesterone bleeding, that is, from the 2nd to 5th day of the cycle, and the medication is taken for 5 days. The starting time has no significant effect on the ovulation rate, pregnancy rate and endometrium. Starting in the early follicular stage can ensure sufficient follicle recruitment. The starting dose of clomiphene is usually 50 mg, but 100 mg is more appropriate for obese women. If there is no ovulation response to the above methods, the next dose can be increased by 50 mg until ovulation occurs. Although the FDA recommends a maximum daily dose of 250 mg, the highest dose commonly used in clinical practice is 150 mg. The lowest dose possible should be used, as higher doses do not improve pregnancy outcomes and may theoretically have a negative impact on endometrial thickness and implantation. If B-ultrasound is used to monitor the maturation of follicles, the dominant follicle is considered a mature follicle when it reaches an average diameter of 18 to 20 mm. For those whose B-ultrasound shows enlarged follicles but who cannot ovulate, human chorionic gonadotropin (hCG) can be used to induce ovulation and guide the timing of intercourse. The ovulation rate of PCOS patients can reach over 80% after using CC, and the pregnancy rate can reach 30% to 60% when used alone. The two most significant side effects of clomiphene are mild ovarian enlargement (13.6%) and multiple pregnancy. Other side effects include hot flashes (10.4%), abdominal distension (5.5%), and rarely visual disturbances (1.5%). Some patients are ineffective with CC treatment, which is called clomiphene resistance. However, the current definition of clomiphene resistance is different. The maximum dose ranges from 150 to 250 mg. After three consecutive cycles of application, there is no ovulation response.

2) Gonadotropin (Gn)

For patients with CC resistance, gonadotropin (Gn) is a commonly used ovulation-inducing drug, including FSH and HMG. Currently, there are various preparations of Gn, such as hMG, urinary FSH and recombinant FSH, but there are problems of high price, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) risks when used. The conventional method starts 3 to 5 days after menstruation, with 1 tube of HMG per day or 75 IU of pure FSH per day. The ovulation rate and pregnancy rate are higher, but the incidence of ovarian overstimulation syndrome (OHSS) and the multiple birth rate are high. Currently, a small-dose slow-increase regimen is mostly used. This method has an ovulation rate of 70% to 90%, a single follicle development rate of 50% to 70%, a cycle pregnancy rate of 10% to 20%, and a low OHSS incidence of 0% to 5%. However, the treatment cycle is long and the patient cost is relatively high.