Polycystic ovary syndrome (PCOS) is a syndrome of endocrine disorders characterized by sporadic ovulation or anovulation, hyperandrogenism or insulin resistance, and polycystic ovaries. Symptoms include sporadic or amenorrhea menstruation, chronic anovulation, infertility, hirsutism and acne. Due to persistent anovulation, in severe cases, the endometrium can become overproliferated, increasing the risk of endometrial cancer. Treatment options are very complex and vary for different symptom improvement and fertility requirements.
Long-term attention is required. Common symptoms include abnormal menstruation, hirsutism, infertility, obesity, acanthosis nigricans, enlarged ovaries, and estrogenic effects. The etiology, including the cause of PCOS, is unknown and the pathological mechanisms involved are very complex. It is generally believed to be related to hypothalamic-pituitary-ovarian axis malfunction, adrenal dysfunction, genetics, metabolism and other factors.
1. Genetic factors
PCOS is an autosomal dominant, or X-linked (companion) inheritance, or a disease caused by genetic mutations. Most patients have karyotype 46, XX, and some have chromosomal aberrations or chimeric types such as 46, XX/45, XO/46, XX/46, XXq and 46, XXq.
2. Adrenal primordial hypothesis
PCOS originates from prepubertal adrenal disease, that is, when stimulated by strong stress, the reticular zone secretes too much androgen, which is converted into estrone outside the gonads, causing feedback disruption of the GnRH-GnH release rhythm of the HP axis and an increase in the LH/FSH ratio, which subsequently causes an increase in ovarian androgen production, that is, the adrenal glands and ovaries jointly secrete more androgens resulting in hyperandrogenemia. Hyperandrogenemia causes thickening of the peritoneal fibrosis and inhibition of follicular development in the ovary, resulting in cystic enlargement of the ovary and chronic anovulation.
According to TCM, this disease is mainly caused by kidney deficiency, phlegm-dampness, qi stagnation and blood stasis, and damp-heat in the liver, resulting in dysfunction of the kidney-tendu-hypophyseal-uterine axis, leading to menstrual arrest and infertility.
Clinical manifestations
1. Abnormal menstruation
Scanty menstruation, amenorrhea, or functional uterine bleeding in a few cases. Most often occurs in adolescence, as irregular menstruation after the first menstruation.
2.Hirsutism
More common, the incidence can reach 69%. Due to the increase of androgen, it can be seen that the hair on the upper lip, jaw, chest, back, middle of the abdomen, both sides of the upper thighs and the perianal area is thickened and increased. At the same time, acne, excessive sebum secretion on the face, low and coarse voice, enlarged clitoris, throat knots and other masculine signs can be observed.
3. Infertility
Due to long-term non-ovulation, patients are often combined with infertility, sometimes there may be occasional ovulation or miscarriage, the incidence can reach 74%.
4.Obesity
The body weight is more than 20%, and the body mass index ≥25 accounts for 30% to 60%. Obesity is mostly concentrated in the upper body, waist / hip ratio > 0.85. Mostly since the beginning of adolescence, gradually aggravated with the growth of age.
5.Echinodermia nigricans
Labia, back of the neck, axilla, under the breast and groin and other parts of the skin folds appear gray-brown pigmentation, symmetrical, skin thickening, soft texture.
6.Ovarian enlargement
In a few patients, enlarged and firm ovaries can be palpated by general gynecological examination, but most of them need ultrasound examination to determine.
7. Estrogen action
Due to the absence of ovulation, progesterone cannot be produced. If the endometrium is stimulated by estrogen for a long time, endometrial hyperplasia, atypical hyperplasia, or even cancer may occur.
Treatment
1. Obesity and insulin resistance
Increase exercise to reduce body weight, correct endocrine metabolic disorders aggravated by obesity, reduce insulin resistance and hyperinsulinemia, reduce IGF-1 and increase IGfBP-1, and increase SHBG to reduce free androgen level. Weight loss can restore ovulation in some obese PCOS patients and prevent the occurrence of type 2 diabetes and cardiovascular disease. Metformin treatment, with or without diabetes, is effective in reducing body weight, improving insulin sensitivity, lowering insulin levels, resulting in hair loss and even restoring menstruation (25%) and ovulation.
Since obesity and insulin resistance are the main causes of PCOS, any drug that can reduce body weight and increase insulin sensitivity can treat this syndrome.
2.Ovulation induction by drugs
(1) Clomiphene is the drug of choice for PCOS, with an ovulation rate of 60% to 80% and a pregnancy rate of 30% to 50%. Clomiphene competes with endogenous estrogen at the hypothalamic-pituitary level for receptors, inhibits negative estrogen feedback, increases the pulse frequency of GnRH secretion, and thus adjusts the ratio of LH to FSH secretion. Clomiphene also directly induces the synthesis and secretion of estrogen by the ovaries. After taking this drug, side effects such as ovarian enlargement due to hyperstimulation (13.6%), bouts of heat due to vasodilation (10.4%), abdominal discomfort (5.5%), blurred vision (1.5%) or rash and mild alopecia have been observed.
During treatment, basal body temperature of menstrual cycle should be recorded to monitor ovulation, or serum progesterone and estradiol should be measured to confirm the presence of ovulation and guide the dose adjustment of the next course of treatment. If there is still no ovulation or conception after 6-12 months of clomiphene treatment, clomiphene plus HCG or glucocorticoids, bromocriptine or HMG, FSH, GnRH can be given as treatment.
(2) Combination of clomiphene and chlortetracycline (HCG) add chlortetracycline (HCG) on day 7 after stopping clomiphene.
(3) Combination of glucocorticoids and clomiphene The role of adrenocorticosteroids is based on their ability to suppress excess androgen secretion from the ovaries or adrenal glands. Dexamethasone or prednisone is usually used, with an efficiency of 35.7% within 2 months and some restoration of ovarian function in amenorrhea without ovulation. If ovulation is not induced with clomiphene, dexamethasone can be added to the treatment cycle.
(4) HMG is mainly used in patients with reduced secretion of endogenous pituitary gonadotropins and estrogens. The risk of ovarian hyperstimulation syndrome (OHSS) is higher.
The dose of HCG should be varied according to the person and the treatment cycle, and close monitoring of follicular maturation should be provided to prevent the development of ovarian hyperstimulation syndrome (OHSS).
(5) Gonadotropin-releasing hormone (GnRH) GnRH can promote the release of FSH and LH from the pituitary gland, but long-term application makes the GnRH receptors in pituitary cells insensitive, leading to a decrease in gonadotropins and thus reducing ovarian sex hormone synthesis. Its effects are reversible, starting with excitatory effects on pituitary FSH, LH and ovarian sex hormones, decreasing to normal levels after 14 days and reaching depot levels in 28 days. However, the clinical application of GnRH-A is limited due to its expensive value and large dosage.
(6) FSHFSH is available in purified and recombinant human FSH (rhFSH).FSH is an ideal therapeutic agent for polycystic ovaries, but it is expensive and may cause OHSS. FSH can also be used in combination with GnRH-A to improve ovulation success.
(7) Bromocriptine is suitable for postprandial administration in ICOS patients with high PRL.
3.Bilateral ovarian wedge resection
It is suitable for patients with elevated blood testosterone, bilateral ovarian enlargement and normal DHEA and PRL (suggesting that the main cause is in the ovaries). Removing part of the ovaries to remove excessive androgen production by the ovaries can correct the disorder of hypothalamic-pituitary-ovarian axis regulation. The pregnancy rate is 50-60%. The postoperative recurrence rate is high, and pregnancy is not favored if complicated by pelvic adhesions. Laparoscopic ovarian cautery or resection can also be effective.
4. Treatment of hirsutism
The hair can be cut off regularly or applied with “hair loss agent”, avoid plucking to prevent stimulation of excessive growth of hair follicles, or electrolysis treatment or application of androgen inhibiting drugs.
(1) Oral contraceptives are better than estrogen-based estrogen and progestin combination tablets, which can inhibit LH secretion, reduce blood testosterone, androstenedione and DHEAS, and increase the concentration of sex hormone binding globulin.
(2) Progestins have weak anti-androgenic and mild inhibitory effects on gonadotropin secretion, and can reduce the levels of testosterone and 17-keto steroids. Medroxyprogesterone (Amnestic progesterone) is more commonly used. It is usually taken orally. In addition, cyproterone acetate (CPA) is a high potency progesterone with strong anti-androgenic effects. It is often taken together with ethinylestradiol.
(3) GnRH-A is used from day 1 to 5 of the menstrual cycle, and a variety of preparations such as transdermal inhalation, subcutaneous and intramuscular injection are now available. The addition of ethinylestradiol can avoid the adverse effects caused by estrogen after the use of the drug.
(4) Dexamethasone is indicated for hyperandrogenemia of adrenal origin and is taken orally every night.
(5) Spironolactone interferes with ovarian androgen synthesis by preventing testosterone from binding to receptors in hair follicles and also by inhibiting 17α-chelatase. It may result in reduced hair growth and thinning of hair in patients. Hyperandrogenemia with anovulatory menstrual disorders can be used on the 5th to 21st day of menstruation, which can restore menstrual cycle and ovulation in some patients.
5.Artificial menstrual cycle
For patients without hirsutism and without fertility requirements, progestin can be given to perform artificial cycle therapy to avoid excessive hyperplasia and cancer of the endometrium.