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Lower body fat

Introduction
Cause
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Diagnosis

Introduction

Introduction Lower body obesity: Different endocrine environments can cause different obesity postures, and estrogen increase is lower body obesity (ie, female obesity). It is a dystrophic disease, which is characterized by excessive accumulation of fat in the body and excessive ratio of adipose tissue to other soft tissues, which is a manifestation of the pathophysiology of polycystic ovary syndrome.

Cause

Cause

Cause of disease

The cause of PCOS is unclear. It is generally considered to be related to hypothalamic-pituitary-ovarian axis dysfunction, adrenal dysfunction, genetics, metabolism and other factors. A small number of PCOS patients have sex chromosomes or autosomal abnormalities, and some have a family history. Recently, it has been found that certain genes (such as CYP11A, VNTR of insulin gene) are involved in the occurrence of PCOS, further affirming the role of genetic factors in the pathogenesis of PCOS.

Pathophysiology

1. Glutamine release abnormalities PCOS patients with elevated blood LH, and FSH normal or decreased, LH / FSH 2 ~ 3, LH may be overreactive after intravenous GnRH, thought to be primary hypothalamic-pituitary dysfunction . Inhibition of GnRH neurons by dopaminergic and opioid peptide neurons in the hypothalamus is out of control, leading to increased LH secretion. But it is more likely to be caused by abnormal feedback inhibition of estrogen. A non-periodic extra-metastatic conversion of estrogen (estrone E1) will result in positive feedback to LH secretion and negative feedback inhibition of FSH secretion. LH stimulates follicular cell proliferation, produces a large number of androgens, and androgen cannot be completely converted into estrogen, further increasing the production of extracellular aromatized E1. Excessive androgen causes follicular atresia, ovarian envelope fibrosis, and thickening of the envelope. Ovulation disorders occur due to a lack of peak LH in the mid-menstrual cycle. In addition, it has been found that the ovary of patients with PCOS may also secrete "inhibin", inhibit the secretion of FSH, affect the development and maturity of follicles, and more cystic follicles. In recent years, hyperinsulinemia and increased IGF have also increased LH secretion. .

2. Too much androgen In PCOS, almost all androgen production increases. Sex hormone-binding globulin (SHBG) is reduced, free androgen is increased, and activity is enhanced. As for the excessive androgen derived from the ovary or adrenal gland, there is a difference. High-dose GnRH agonists reduced gonadotropin, androstenedione and testosterone, but had no effect on DHEAS derived from the adrenal gland. About 70% of PCOS patients are reported to be caused by ovarian-derived androgens:

1 due to dysfunction of enzymes required by steroid hormones, such as aromatase deficiency, 3-ketoxime dehydrogenase deficiency or decreased activity, P45OC17A regulation abnormalities, estrogen synthesis disorders, a large number of androgens in the periphery (fat, liver, kidney ) converted to estrone. It has also been suggested that insufficient ovarian development leads to a decrease in the activity of aromatase.

2LH pulse frequency and amplitude increase, stimulate the proliferation of follicular cells and mesenchymal cells and the production of androgen. Excessive androgen promotes follicular atresia, ovarian granulosa cells are initially flavinated, growth stops, and ovulation cannot occur, forming PCOS.

This disease occurs mostly after menarche in menopause, presumably due to premature maturation, adrenal dysfunction, and continued secretion of excessive androgen. In addition, various androgen levels in ovarian and adrenal venous blood were measured before and after application of dexamethasone. The results support the ovary and adrenal gland as a common source of PCOS excess androgen, and found that 50% of PCOS patients have adrenal-derived androgen increase. .

3. Excessive estrone PCOS women with progesterone and other drugs have withdrawal uterine bleeding, taking chlorpheniramine can lead to follicular mature ovulation, menstrual cramps, suggesting that PCOS patients not only high androgen levels, but also increased estrogen. In vivo active estrogens include estradiol (E2) and estrone (E1), E2 is mainly derived from the ovary, and E1 is derived from the transformation of the ovary, adrenal gland and surrounding tissues. PCOS patients with non-periodic E1 increased significantly, E1/F2 ratio increased (normal E1/F2 1), especially in obese people with more fat, aromatase activity, peripheral tissue conversion increased, E1 level can be higher, and source E1 in peripheral tissues is not regulated by pituitary gonadotropins, and there is no periodic change. The continuous high level of estrogen feedback regulation of the hypothalamus-pituitary is not normal.

4. Cytochrome P450C17A dysregulation PCOS The main defect is the hypothalamic-pituitary receiving abnormal feedback signal. This may be related to the autocrine and paracrine regulation mechanisms of the ovary and adrenal gland itself. Patients with PCOS are often associated with elevated 17-hydroxyprogesterone (17-OHP) due to abnormal regulation of P450C17A in the intracellular or adrenal reticular band of the ovarian follicle. P450C17A has dual activities of 17-hydroxylase and 17,20-streptase, converting progesterone to 17-OHP and androstenedione at 4, and pregnenolone to 17-hydroxyprene at 5 Alcohol ketone and DHEA. 17-hydroxyprogesterone is an important precursor for the synthesis of cortisol from the adrenal gland. It is also an important precursor of ovarian synthetic hormones, especially androgens. 17-hydroxyprogesterone and androstenedione were significantly elevated in patients with PCOS given GnRH-A or HCG (especially after inhibition with dexamethasone); the ACTH stimulation test also promoted the simultaneous increase of DHEA and 17-OHP in the adrenal gland. It is suggested that the activity of P450C17A in the ovarian and adrenal reticular bands is increased. Therefore, abnormal regulation of P450C17A activity is an important cause of excessive secretion of androgen in the adrenal gland and ovary. However, it is unclear why abnormal regulation of steroid synthesis occurs. The insulin/IGFs system stimulates ovarian and adrenal P450C17A mRNA expression and its activity. In addition, the coding region of the side chain lyase gene of CYP11A is associated with the production of excess androgen.

5. Insulin resistance and hyperinsulinemia PCOS patients with or without obesity, have varying degrees of insulin resistance and hyperinsulinemia. It has recently been found that approximately half of patients with PCOS are associated with defects in insulin receptor serine phosphorylation. Therefore, insulin is considered to play an important role in its pathogenesis. Insulin and IGF-1 act on the ovarian membrane cells through the IGF-1 receptor, promoting the synthesis of androstenedione and testosterone. Recent studies have found that insulin receptors in the vicinity of the pituitary, or the presence of high IGF-1 hyperemia can promote LH-stimulated follicular cell proliferation, leading to excessive androgen and premature occlusion of follicles. Hasegawa's treatment of PCOS with the insulin sensitizer Troglitazone supports a reduction in insulin levels and a corresponding decrease in LH and androgen levels. Elevated insulin plays an important role in regulating the metabolism of SHBG, which can reduce the production of SHBG in the liver and increase the free testosterone. In addition, insulin receptor serine phosphorylation inhibits insulin receptor activity and promotes the 17,20-streptase activity of P450C17A. In recent years, a 5'-terminal variable number tandem repeat sequence (VNTR) of the insulin gene located on chromosome 11pl5.5 found that the VNTR of the insulin gene is a major susceptible site of PCOS (especially ovulation PCOS). This indicates that the insulin VNTR polymorphism is a genetic factor of PCOS.

6. Obese PCOS with obesity (BMI 25) accounted for 20% to 60%. Body fat distribution is uneven. Adipose tissue is known to be an important metabolic site for steroid hormones, and aromatase in adipose tissue converts peripheral androgens to E1 and E2. Studies have confirmed that the amount of androstenedione converted to E1 is related to the total amount of adipose tissue. In hyperandrogenemia, SHBG decreases and free E2 increases. Estrogen causes fat cells to grow and proliferate. Different endocrine environments can cause different obesity postures, elevated androgen expression is upper body obesity (ie, male type obesity), and estrogen increase is lower body obesity (ie, female type obesity). Weight gain is often accompanied by an increase in blood insulin and a decrease in SHBG and IGFBP, resulting in an increase in free sex hormones and IGF-1. These patients are often accompanied by impaired glucose tolerance or type 2 diabetes. Recently, Rouru et al. proposed that the obesity-leptin-NPY axis may be the cause of excessive secretion of hypothalamic-pituitary-LH in some patients with PCOS, that is, the secretion of leptin in obese women is increased, and the latter inhibits the expression of NPY mRNA and NPY in the hypothalamus. The inhibition of LH by NPY prompted a large release of LH.

7. Hyperprolactinemia The relationship between hyperprolactinemia and PCOS remains to be further studied. The incidence of PCOS hyperprolactinemia was 10% to 15%, but the PRL of patients diagnosed with PCOS was mildly or moderately elevated. Higher levels of PRL were associated with pituitary PRL tumors. The mechanism that causes high PRL is unclear. May be: 1 elevated PRL is associated with increased blood estrone. 2 hypothalamic dopamine is relatively insufficient, and treatment of PCOS anovulatory or hirsutism with dopamine agonists (such as bromocriptine) can be successful. Patients with high PRL have no response to exogenous gonadotropins. 8. PCOS and ovarian autoimmunity studies have found that some PCOS are associated with ovarian autoimmunity. There are lymphocytic infiltration in the follicles of PCOS patients, and anti-ovarian cell antibodies exist, but Rojansky et al.'s study of 31 patients with PCOS showed that anti-ovarian antibodies were not associated with PCOS. Luborsky et al used enzyme-free analysis to detect anti-ovarian antibodies in 24 PCOS patients, and 25% of PCOS patients were positive. The positive rates of menopausal women and women of childbearing age were 22% and 19%, respectively. There was no difference in the positive rates of the three groups. Therefore, there is no consistent conclusion about whether PCOS is related to ovarian autoimmunity.

9. The relationship between polycystic ovary syndrome and blood pressure, patients with polycystic ovary syndrome have hyperandrogenism and hyperinsulinemia, which can directly cause macrovascular damage and improve sympathetic nerve excitability and cause hypertension. Hypertension occurs more frequently in patients with polycystic ovary syndrome. There are also studies that the systolic blood pressure of obese patients with polycystic ovary syndrome is significantly higher than that of patients with wasting and normal age. Patients with polycystic ovary syndrome have hyperandrogenism and hyperinsulinemia, which can directly cause macrovascular damage and increase sympathetic nerve excitability to cause hypertension. Hyperinsulinemia can cause disorders of glucose and lipid metabolism, produce obesity, affect blood. Viscosity, causing high blood pressure. Therefore, the treatment of polycystic ovary syndrome is mainly aimed at improving insulin sensitivity and reducing hyperandrogenism, reducing body weight, improving disorders of glucose and lipid metabolism, and reducing blood viscosity and other primary diseases.

Ovarian pathology: typical PCOS patients have bilateral ovarian symmetry, volume up to 2 to 4 times normal, surface wrinkles disappear, smooth, grayish white, rich in blood vessels, thick capsule, and a large amount under the capsule The follicles of different sizes can reach a maximum diameter of 1.5cm, the wall of the capsule is thin, and the follicular cells around the vesicles proliferate with luteinization. The thickening of the capsule is the result of long-term non-ovulation, the thickness of the capsule and the level of blood LH and masculinity. Positive correlation.

Examine

an examination

Related inspection

Urinary transferrin

1. Clinical diagnosis After menarche, menstruation is still irregular, menstrual scarcity and (or) amenorrhea, accompanied by obesity and hairy, infertility after marriage, etc., should be suspected of PCOS. Typical cases have various symptoms and signs mentioned above, namely menstrual disorders, hairy, acne, obesity, infertility and the like. Atypical cases can be expressed as:

1 simple amenorrhea without obesity, hairy and ovarian enlargement, exclude other diseases, and those with positive progesterone test should still consider PCOS.

2 ovulatory dysfunctional bleeding.

3 menstrual abnormalities combined with hairy.

4 menstrual abnormalities with masculine symptoms, no obvious obesity.

5 dysfunctional uterine bleeding with infertility.

For atypical cases, detailed information about the medical history, such as age of onset, growth and development, onset of illness, history of medication, family history, personal habits, and general systemic diseases are required. Combined with auxiliary examination, exclude other diseases, and confirm the diagnosis by B-ultrasound and other tests.

2. Diagnostic criteria Due to the heterogeneity of the disease, the diagnostic criteria have not been unified. Most scholars have combined with an androgen level according to the onset of puberty, abnormal menstruation and ovulation, hairy, blood LH and/or LH/FSH ratio. High, ultrasound examination of polycystic ovary signs, after the exclusion of other similar diseases, can determine the diagnosis of this disease. The Reproductive Endocrine Committee of the Japanese Obstetrics and Gynecology Society proposed the diagnostic criteria for PCOS in 1993 as follows:

(1) Clinical symptoms: 1 menstrual abnormalities (amnesom, thin menstruation, anovulatory menstruation, etc.); 2 masculinization (hairy, acne, low-pitched voice, clitoris hypertrophy); 3 obesity; 4 infertility.

(2) Endocrine examination findings: 1LH high value, FSH normal value; 2 LH secretion increased after injection of GnRH, FSH secretion was normal; 3 estrone/estradiol ratio increased; 4 blood testosterone or androstenedione increased .

(3) ovarian findings: 1B super-see multiple follicular cystic changes; 2 double diagnosis and B-ultrasound see ovarian enlargement; 3 laparoscopic ovarian intimal hypertrophy and surface bulge; 4 microscopic observation of follicular cell layer hypertrophy Proliferation and interstitial hyperplasia.

The above items (1), (2), and (3) are mandatory items. When all three items are available, they can be diagnosed as PCOS. Other items are used as reference. If all necessary and reference items are available, it is a typical PCOS. Case.

In addition, the diagnostic criteria proposed are as follows:

(1) Clinical symptoms: including: 1 amenorrhea (more than 60 days); 2 functional uterine bleeding or persistent anovulation (more than 3 months); 3 infertility; 4 masculinizing signs; 5 obesity.

(2) Therapeutic diagnosis: once amenorrhea, with clomiphene or plus HCG therapy, starting on the 5th day of the menstrual cycle, clomiphene 50mg / d, and even served for 5 days, more can restore ovulation. In case of ineffectiveness, HCH1000U can be added on the 2nd to 4th day after stopping clomiphene, once/d for 3 days. No ovulation is observed after 3 courses of treatment.

(3) Endocrine examination: including: 1 high blood LH (20 ~ 50mU / ml) and GnRH overreaction, blood FSH in the normal range or lower; 2 blood testosterone increased (60% or more); 3HMG (human menopause) Gonadotropin) 225 U / d, after 3 days, on the 6th day of administration, the estrogen in the urine increased excessively (150g / 24h or more); 4 dexamethasone 4mg / d, oral, on the 5th day Increased urinary 11-deoxy-17-ketosteroids (600 g / 24 h or more).

(4) ovarian morphology (including endoscopic findings): visible to the naked eye: 1 no fresh corpus luteum formation; 2 ovarian capsule thickening; 3 ovarian enlargement; 4 cystic enlarged follicles juxtaposed under the capsule. Tissue findings: Follicular cells and interstitial cells luteinized.

Laboratory inspection:

1. LH/FSH blood LH and FSH ratio and concentration were abnormal, non-periodic secretion, LH increased in most patients, and FSH is equivalent to early follicular phase, LH / FSH 2.5 ~ 3. Many scholars believe that the increase in the proportion of LH/FSH is a feature of PCOS.

2. Male steroids and androgen are too much, testosterone, androstenedione, DHEA, DHEAS levels can be increased.

3. Female steroid estrone and estrogen abnormalities, constant estrogen levels, E2 level fluctuations, no normal menstrual periodic changes, E1 levels increased, E1/E2>1.

4. PRLPCOS can be mildly elevated, but PCOS symptoms can occur due to hyperprolactinemia and should be identified.

5. Increase in urinary 17-OHCS and 17-KS24h urinary 17-ketone reflects an increase in adrenal androgen secretion.

6. Dexamethasone inhibition test can inhibit the secretion of adrenal hormones, take dexamethasone 0.5mg, once every 6 hours for 4 days, take blood samples after taking, such as serum dehydroepiandrosterone sulfate or urinary 17-ketosteroids Being inhibited to normal levels may rule out the possibility of adrenal tumors or hyperplasia.

7. Chorionic gonadotropin (HCG) stimulation test HCG stimulates ovarian synthesis of androgens, and injection of HCG can cause elevated plasma androgen levels.

8. Corticotropin (ACTH) Excitatory Test ACTH stimulation test can promote the increase of adrenal gland androgen DHEA and urinary 17-KS. The HCG stimulation test, the dexamethasone inhibition test, and the ACTH stimulation test can help identify the source of androgen elevation.

9. Vaginal exfoliation cell maturation index is an easy way to understand the status of sex hormones in the body. A smear of excessive testosterone tends to have a three-layer cell type at the same time. When the concentration is significantly increased, the number of cells in the three layers is almost equal, but it must be distinguished from inflammation. Estrogen levels can be estimated from the percentage of superficial cells, but do not reflect the amount of hormones in the blood.

10. The basal body temperature is measured to determine whether there is ovulation, the ovulator is biphasic, and the ovulatorless is generally single-phase.

Other auxiliary inspections:

Pelvic B-ultrasound

2. Pneumopers

3. Laparoscopy (or surgery)

4. Transvaginal high-resolution ultrasound examination

5.CT, MRI

Diagnosis

Differential diagnosis

Centripetal obesity: A special form of body produced when glucocorticoids persist in the body. Because glucocorticoids have different effects on adipose tissue in different parts of the body: the decomposition of fat tissue in the limbs is enhanced and the fat synthesis in the abdomen, face, shoulders and back is increased, so that a kind of facial mellow, back hypertrophy, waist width and abdomen are present. Spherical bulge, the fat body of the proximal extremities is thick and the distal end is thin, and the body is not symmetrical.

Water, sodium retention obesity, also known as idiopathic edema. This type of obesity is more common in reproductive and menopausal women. Its occurrence may be related to increased capillary permeability, increased aldosterone secretion and slowing of venous return due to increased estrogen. The fat is unevenly distributed, mainly in the calf, thigh, hip, abdomen and breast. The weight gain is rapid, and it is closely related to the body position. The tiredness and standing weight increase, and the rest and lying down are relieved. In the morning and evening, the normal weight change is 0.4 kg, and the patient's weight changes in the morning and evening are more than 1 kg. The edema of the disease is often cyclical, morning face, eyelid edema, activity after getting up, lower limbs, trunk gradually edema, weight before dinner increased by 1.2 ~ 4.5 kg before breakfast, an average of 2.4 ± 0.7 kg. The vertical position water test showed that the patient had water and sodium retention.