Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome
[Summary]



Polycystic ovary syndrome (polycystic ovary syndrome, PCOS; Stein-Leventhal Syndrome; sclerocystic ovary disease) is chronic anovulation, and amenorrhea, menstruation or dilute hair, infertility, obesity, hirsutism and polycystic ovarian increases for the clinical characteristics of the Comprehensive syndrome. Polycystic ovary syndrome, is a multi-endocrine axis dysfunction caused by disease final ovarian pathological changes its initial neuroendocrine change is the release of GnRH-GnH increase in the frequency and pulse amplitude, LH / FSH ratio increased.



[Diagnosis]




Diagnosis including the seizure is a typical PCOS, the so-called Stein-Leventhal syndrome, the diagnosis is not difficult, Ran atypical clinical多见who should make the necessary checks and experimental ovarian pathology.

A hormone Determination

(1) gonadotropin: About 75% of patients with elevated LH, PSH normal or decreased LH / FSH ≥ 3.

(B) steroids

1. Androgen, testosterone, dihydrotestosterone, thin-dione and 17 ketones steroids increased. As SHBG reduction will enable free androgen increased.

2. Estrogen total up to 140 pg / ml, the early follicular-diol equivalent level of about 60 pg / ml, extragonadal estrone to generate increased E1/E2 ≥ 1.

3. Adrenal DHEAS generate increased plasma concentration of ≥ 3.3 μ g / ml, 17-hydroxy progesterone also increased (normal <200 ng / dL), Ran if ≥ 800 ng / dl should consider late-onset congenital adrenal hyperplasia, 21 hydroxylation β-or 11-hydroxylase deficiency. If the 200 to 800 ng / dl, should be ACTH test (Cotrosyn0.25mg iv) 60 minutes after injection increased to 17-hydroxy progesterone for congenital adrenal hyperplasia.

(C) prolactin (PRL): About 25 to 40% of the patients ≥ 25 ng / ml, respectively.

(D) insulin (insulin); fasting insulin increased ≥ 14 mu / L, IGF-I increased (the normal 120 mmol / L), plasma IGF-I binding protein decreased (normal <300 ng / mL).

(5) A melanocortin-yuan (proopiomelancortin, POMC) and its derivatives: β-promoting lipid-, β-endorphin and increased β-MSH, normal or elevated ACTH. GH and TSH normal.

Second, ultrasonic inspection

Bilateral polycystic ovarian increased biofilm thickness strong echo. Biofilm visible a few days more, 2 to 7 mm in diameter cystic follicles. Mesenchymal echo uneven ovarian, endometrial hypertrophy, attention should be excluded uterine and ovarian tumor and adrenal lesions.

Third, retroperitoneal inflatable angiography and Hysterosalpingography

Objective To observe the ovaries and adrenal shape, the size, to identify the reasons for re-Kaohsiung hormone hyperlipidemia.

Fourth, consultation scratches and the seizure of endometrial

Where patients ≥ 35 years of age, should be conventional diagnosis of endometrial scratches and seizure, in order to understand changes in endometrial tissue (glands cystic / adenoma type / atypical hyperplasia), and to remove endometrial carcinoma.

5, endoscopic

Including endoscopic and laparoscopic lacunae, to direct observation of ovarian morphology or to biopsy, puncture, wedge resection, and the tracks, and other treatment.

6, CT and MRI

Except to identify and pelvic tumors.

7. Laparotomy

Diagnosed with ovarian cancer or ovarian wedge resection to visit when implemented.


[Treatment]




1, infertility treatment

That ovulation treatment, including reasonable diet improved insulin Jugang management, drug ovulation and laparoscopic surgical treatment and treatment technology.

(1) Catering Management: focus on reducing carbohydrate / fat intake rate to contain insulin Jugang, reducing weight to stabilize abnormal androgen secretion and gonadotropin (Pasquali 1986).

(B) Drug ovulation: chlorine Di phenol-amine (Clomiphene citrate, CC) mainly due compatibility and other ovulation drugs.

1. Chlorine Di phenol-amine (CC): ovulation induction of preferred drugs, the use of simple, safe and effective as an anti-estrogen to the hypothalamus - pituitary level and competitiveness of endogenous estrogen receptor, responsible for the inhibition of estrogen-fed, GnH arising from the release of GnRH-increase trigger ovulation, and directly promote ovarian steroid hormone production (Kerin 1985).

Methods: menstrual cycle (or progesterone withdrawal bleeding) started the fifth day to 200mg daily oral CC50, and even served five days, the daily maximum dose of not more than 250 mg. Avoid high-stimulation syndrome (ovarian hyperstimulation syndrome, OHSS). Above treatment for 3 to 6 cycles and monitoring ovulation and pregnancy.

2. Tamoxifen: CC applicable to the treatment were invalid. Tamoxifen is an anti-estrogen, short-term low-dose therapy can promote ovulation, the same mechanism CC.

Methods: menstrual cycle (or progesterone withdrawal bleeding) on the second day (or fifth) 20 ~ 40 mg / d, and even served five days. Therapeutic effects similar to CC.

3.CC-hCC: CC not only applicable to trigger ovulation or merger of luteal function-are not. Namely, the completion of CC50 ~ 200mg / d × 5 after treatment, in 15 days of the menstrual cycle, an intramuscular injection hCG5000 ~ 10000 units, or ultrasound monitoring of follicular development in the once follicles ≥ 18 mm in diameter, serum E2 ≥ 300 to 500 pg / ml hCG injection the next day.

4.CC-dexamethasone: PCOS apply to the merger of Kaohsiung hormone levels, which increased plasma testosterone and DHEAS are. Dexamethasone is 0.5 mg / d,临睡前taking, the group ovulation rate of 50%.

5.hMG-dexamethasone: CC applicable to the treatment ineffective, hyperlipidemia, and low gonadotropin hormone hyperlipidemia, Kaohsiung. 81% of their ovulation rate, the pregnancy rate 75 per cent.

6.hMG-hCC: CC applicable to the treatment ineffective hyperlipidemia, and low gonadotropin. HMG75 ~ 150u / d at the beginning of the fifth day menstrual cycle intramuscular injection, and monitoring of follicular development in the ultrasound and serum E2 Once the bubble timely reaching maturity after hCG injection.

7. Purified FSH (pure FSH)-hCG: pFSH is intended to reduce the mature egg follicle development and the process of Kaohsiung high LH hormone and the adverse effects of hyperbilirubinemia, and improve the LH / FSH ratio. Recent clinical data indicate that in the application of GnRHa PCOS desensitization after pFSH alternative hMG does not significantly improve the success rate of IVF, the treatment of the group pending further observation.

8.GnRHa-hMg-hCG: GnRHa application designed to promote pituitary desensitization to prevent menstruation early and mid-LH peak prematurely luteinized follicular (premature luteinization) and Kaohsiung hormone level hyperlipidemia. GnRHa PCOS to four weeks after treatment plasma androgen levels can be reduced to after castration, but do not affect the source of adrenal androgen secretion. The group of three cycle pregnancy rate of 77% higher than that of hMG or HCG treatment group.

9. Pulse GnRHa therapy: apply to low gonadotropin hyperlipidemia, ran on PCOS patients with no obvious effect. Impose the group after treatment that LH and testosterone increased ovulation rate 38% pregnancy rate of 8%.

(C) treatment technologies: Group reported only two applications IVF / ET PCOS infertility treatment. DaLe (1991) 44 on the treatment of a GnRHa-hMG promoting super-follicle generation, mining cycle egg 9 ~ 18.8 ± 19.3 ± 6.1, embryo transfer pregnancy rate of 33 percent. However, due to the elimination cycle OHSS caused by rate (Canceled cycle rate) to 24.13% (14/58), the treatment technology in the treatment of PCOS value yet in-depth study.

Second, treatment

Including ovarian wedge resection of the microscopic and laparoscopic surgery.

(1) of ovarian wedge resection (ovarian wedge resection, OWR): treatment of PCOS OWR the exact mechanism is not yet very clear. There are two reported in the literature, OWR three to four days after the serum To, Adione, E1, E2 decreased significantly since LH and FSH dropped unchanged, two weeks after LH / FSH ratio has emerged resume normal follicular development and ovulation. OWR ovulation rate of 80%, 50% pregnancy rate, the rate of postoperative adhesions (41% Buttram 1975). Application of new technologies and new microsurgical adhesion shielding (new adhesive barrier method). Can effectively prevent postoperative adhesions.

(B) Treatment of laparoscopic ovarian (Laparoscopic ovarian treatment): a new technology. That the application of laparoscopic ovarian more pecked excision biopsy (multiple punch biopsy resection, MPBR), ovarian fulguration (ovarian cauterization) and ovarian multi-point laser vaporization (multiple ovarian vaporization) and laser cutting wedge.

Third, hirsutism and Kaohsiung hormone treatment of hyperlipidemia

PCOS, hirsutism incidence of 20 to 80%, and the extent of non-synchronous Kaohsiung hormone hyperlipidemia, with a 5 reductase activity related. Their treatment, according to sources Kaohsiung hormone (ovarian or adrenal) and hirsutism level (light, medium, heavy) choose a different medication.

(1) of the ovarian hormones Kaohsiung hyperlipidemia: use of oral contraceptives (OC), and GnRHa and Ketoconazole (Competition-α receptor antagonist drug imidazoline imidazole derivatives).

OC negative feedback inhibition of GnRH-GnH release, in order to reduce ovarian androgen production, and promote synthesis of SHBG, and to reduce the concentration of free testosterone, and contain endometrial hyperplasia in the treatment of mild, medium hirsutism.

GnRHa the pituitary desensitization and demotion role inhibit ovarian androgen production, for the treatment of severe hirsutism, to be long-term treatment.

Ketoconazole by blocking the activity of cytochrome P450-dependent inhibition of ovarian and adrenal androgen production, the dose of 500 ~ 600 mg / d for at least six months. Deputy reaction was liver and kidney damage.

(2) of the adrenal hormone Kaohsiung hyperlipidemia: The main use of glucocorticoid treatment and Ketoconazole. Glucocorticoid negative feedback inhibition ACTH release to curb production of adrenal-hung, efficiency 26%.

(C) anti-androgen drugs: including antisterone (spiral lactone spironolactone), acetic acid Saipulong (cyproterone acetate, CPA) and perfluorocarbons amide (Flutamide).

Antisterone for aldosterone antagonist and with a variety of anti-androgen activity, such as the suppression of testosterone production, increased testosterone to E1 conversion, antagonistic reductase activity and a 5-receptor (1986). The dose range of 75 to 200 mg / d. Efficiency 72%. Substantial long-term treatment for menorrhagia reaction and 65% of inter-menstrual bleeding 33%.

CPA for 17-hydroxy progesterone derivative, androgen receptor antagonist, inhibited the release of GnH-and ovarian-generation and increased testosterone MCR. Its half-life longer Guchang compatibility ethinylestradiol (EE2) for OC (CPA2mg + EE235 ~ 50 μ g, Dianette / Diane) applications, or compatibility with the natural estrogen (sequential) applications, such as CPA50 ~ 100 μ g / d in the first menstrual cycle taking five to 14 days, at the same time to EE235 ~ 50 μ g or 17 β-E2100 μ g / d, 5 ~ 24 days use. Long-acting injection formulation of 300 mg / month (Marcondes 1990). Large doses (> 100 mg / d) faster onset of action, small dose (2 ~ 20 mg / d) Validity slow.

Amide-fluoride-receptor antagonist only, without affecting serum androgen concentrations (To, FTo, △ 4 dione, DHEAS and E2, SHBG). 250 mg daily dose of 2 to 3 times OC should be compatible, so as to avoid unwanted pregnancies and female male births.

(D) Treatment of hirsutism drug choices: ① mild: OC; ② of disorders / severe: antisterone + OC; CPA + OC; fluoride amide + OC. In addition to drug treatment, the local beauty treatment is necessary.


[Etiology:




1, genetic factors PCOS is a autosomal dominant inheritance, or a chain of X (with) nature of the genetic, or caused by the mutation of diseases. Most patients karyotype 46, XX, some patients with chromosome aberrations or mosaicism as 46, XX/45, XO; 46, XX/46, XXq and 46, XXq.

Second, the initiative adrenal hypothesis Chom (1973) that originated in New PCOS before adrenal disease, that is, when stimulated by the strong stress mesh with excessive androgen secretion, and extragonadal into estrone, and the feedback from HP GnRH-axis GnH release dysrhythmia, LH / FSH ratio increased, the secondary cause ovarian androgen production increased, that is common adrenal and ovarian androgen secretion more of a hormone Kaohsiung hyperlipidemia. Kaohsiung hyperlipidemia in ovarian hormones caused within the biofilm thickness fibrosis, inhibition of follicle and egg, resulting in ovarian cystic increased and chronic anovulation.


[Pathological changes:




Polycystic ovary was typical of many bilateral sclerosis cystic degeneration. Ovarian was a general concept fibrosis or collagen thickening, tenacity, smooth, and a color or gray oysters enhanced luminescence. Than normal volume increased 2 ~ times.

Ovarian profile that envelope under a multitude 2 to 7 mm in diameter cystic follicles or follicular cysts greater retention. Follicular granulosa cells in the microscope less and sparse, theca cell hyperplasia. Atretic follicles increased, a very rare yellow-and-white.


[Clinical]




First, menstrual disorders performance for the primary amenorrhea was only 5%, and 51 ~ 77% of the patients, showing for the secondary amenorrhea, or delay in the normal age at menarche, menstrual then dilute hair, or less, after amenorrhea. Still, 12 percent of menstruation, and the credit luteal unhealthy blood with 22 ~ 29%.

Second, 74 percent of infertility (35 ~ 94%) is due to chronic anovulation.

Third, more than 69% of gross (17 ~ 83%), was particularly prevalent in the lips and lower cheek side of the lower abdomen, based on the medial and lateral leg Unit, and with acne, excess fat and alopecia. Furry and Kaohsiung hormone hyperlipidemia non-synchronous. (Lobo 1983).

4, obesity 41% (16 ~ 49%), more than before puberty begins, progressive, and Kaohsiung this hyperlipidemia assimilation and gonadal hormone estrogen promotes cell, the result of obesity.

5, ovarian hyperplasia 50 ~ 75%, bilateral symmetry Polycystic increase 2 to 4 times, or uterine volume 1 / 3 to 1 / 4 of polycystin-also 20 to 30 percent of ovarian not by big was hardening.

6. Complications According to statistics ≤ 40-year-old patients with endometrial carcinoma in 19 ~ 25% merger PCOS. About 14% of PCOS in progress for the 14-year-old with endometrial carcinoma.


[Diagnosis]




PCOS should pay attention to the cause amenorrhea, hirsutism and other diseases ovarian increase of identification:

A masculine ovarian tumor

Including support for a stromal cell tumors, tumor cell door, lipid cell tumor, and blastoma, traces of adrenal tumors, luteal tumors, and metastatic cancer teratoma. In addition to the above of blastoma, the other sustained tumor growth substantive unilateral tumor, androgen secretion was autonomy, masculine obvious symptoms, and accompanied ascites and metastasis.

Second, adrenal diseases

Including congenital adrenal hyperplasia, adenoma and carcinoma. After two major secreted Androstenedione and DHEA, also independent of secretion from ACTH to promote and dexamethasone suppression. And congenital adrenal hyperplasia, 21 hydroxylase deficiency, a typical genital - urogenital sinus malformation with Xingqi stunted.

Third, thyroid disease

Including hypothyroidism and hyperthyroidism. Hyperthyroidism, T3, T4, SHBG increased androgen metabolic clearance rate decreased by increased plasma testosterone masculine and menstrual disorders. A low, androgen into estrogen to increase by no ovulation.

Fourth, genetic hirsutism

A family history, only simple hirsutism without PCOS symptoms and signs. Normal fertility.

5, ovarian theca cell hyperplasia (ovarian hyperthecosis)

The gonadotropin secretion of normal ovarian not increased, but theca cells were nest (Island) hyperplasia, plasma androgen increased significantly, with serious masculine. Di chloro phenol in the treatment of non-sensitive.

6, insulin Jugang syndrome and melanoma acanthoma

As a fat Island receptor defects diseases (A / B), there will be similar to the PCOS symptoms and signs. Its significant feature is that hyperinsulinemia and neck, axilla melanoma acanthoma.

7. Hyperprolactinemia

Amenorrhea, Yiru, infertility, PRL and DHEAS increased masculine not obvious symptoms, ovarian normal.