2012-05-19
Sex hormones
Four sex hormones controls females menstrual cycle: two polypeptides, FSH (follicle-stimulating hormone) and LH (luteinizing hormone), and two steroids, E2 (estradiol) and PHN (progesterone). FSH anf LH are synthesized by cells of anterior pituitary. Ovaries synthesize E2 and PGN. Sex hormones are secreted in a complex cyclic manner, according to the time of the day and episode rhythm. At pubescence the highest level of circulated sex hormones is found during rest compared with active period of the day. Most of the information is obtained when FSH, LH and E2 tests are performed on days 3-5 of the menstrual cycle, and PGN test – on day 19-23 of the menstrual cycle.
Follicle-stimulating hormone (FSH)
FSH determinates development of ovaries and testicles (gonad tissue). In females FSH stimulate follicle development and maturation in ovaries and enhance secretion of estrogens (estradiol). In males FSH stimulates maturation and release of sperm cells
Steroid hormones through hypothalamus controls FSH secretion. The highest FSH secretion is observed in the middle of menstrual cycle, yet it is lower and shorter than LH secretion.
FSH test is important to distinguish primary insufficiency of sex glands from secondary, caused by pituitary diseases (in case of primary insufficiency FSH concentration increases). FSH test helps to monitor ovary function in the early follicular stage and postmenopausal period (in menopause FSH concentration increases due to obsolescent ovary function and decrease of estradiol concentration). Assessment of this hormone is important in case of infertility and evaluating sexual development of both females and males. FSH usually is determined together with LH (luteinizing hormone).
Venous blood is used for test which is performed daily.
Luteinizing hormone (LH)
LH stimulates ovulation of mature follicles and promotes synthesis of estradiol (and also other estrogenes) and progesterone. Increase of LH concentration in the middle of menstrual cycle shows that ovulation should occur within 24 hours. In males LH stimulates testosterone production.
LH test is important to evaluate function of sex glands and to diagnose infertility. LH concentration increases in case of primary sex glands dysfunction, in menopause it increase due to decreased estradiol and progesterone secretion, and it also increase in girls with ovaries development disorders.
In pituitary gland diseases disorder of secretion of LH hormones occurs among the first. Anorexia nervosa, poor nutrition, severe disease reduces LH secretion. Delayed start of LH and FSH synthesis is observed in case of sexual development retardation and constitutional development syndrome. Episodic changes in LH secretion are higher than FSH. LH may crosswise react with hCG (human chorionic gonadothropin), and therefore LH measurement could be inaccurate in pregnant, parturient woman and in case of hCG-producing tumors.
Venous blood is used for test which is performed daily.
Estradiol (E2)
It is the most active hormone in premenopause, it is synthesized only in ovaries. Another two compounds with estrogen activity, E1 (its higher levels in female body are observed after menopause) and E3 (produced in placenta during pregnancy) are products of estradiol metabolism.
Testosterone is estradiol predecessor. Active enzyme system in ovaries promotes androgen (male sex hormones) conversion to estrogen (female sex hormones). Most of the blood estradiol is conjugated with SHBG (sex hormone-binding globulin), small part binds with albumin and only 2-3% of hormone is free.
Although estrogens affect activity of almost all tissues, their main function is stimulation of the development and maturation of female reproductive system and promotion of reproductive potential. They stimulate development of follicle, uterine mucosa, formation of secondary sex characteristics, control menstrual cycle and promote pregnancy.
Estrogens are important for the normal bone mineral metabolism. Estradiol promotes calcium retention in bone tissue; therefore decrease level of this hormone is associated with osteoporosis risk.
E2 test is important to diagnose disorders of menstrual cycle, female sexual maturation, solve fertility problems, evaluate treatment efficacy. E2 concentration increases when various ovarian tumors occur. Low E2 levels along with increased FSH and LH concentrations show primary ovarian insufficiency.
Estradiol is metabolized in liver, and therefore live function influence final E2 blood concentration (E2 concentration increases in case of liver cirrhosis). In males E2 production increase with the increase of years because androgen secretion weakens.
Venous blood is used for test which is performed daily.
Progesterone (PGN)
Progesterone is produced by ovary corpus luteum (in pregnant woman), placenta (during pregnancy) and suprarenal gland (both in males and females). Progesterone is metabolized in liver. Together with E2 progesterone controls phases of menstrual cycle. Its concentration increases after ovulation (during luteal phase) and decreases four days before menses. PGN test helps to identify ovulation and evaluate function of the corpus luteum.
Placenta produce progesterone during pregnancy. PGN concentration gradually increase and throughout pregnancy and reaches its peak before delivery. PGN promotes secretion activity of uterine mucosa necessary for the implantation of ovum and maintain uterus quiescence by inhibition of oxytocin production. PGN stimulates growth of breasts.
It was established that PGN concentration < 5 ng/mL is reliable marker of unviable pregnancy. Follow-up an other diagnostic procedures are necessary when progesterone concentration is between 5 and 25 ng/mL. Venous blood is used for test which is performed daily.
Prolactin (PRL)
Prolactin is polypeptide hormone released by pituitary gland. Its primary function is control of mother’s milk production. Breastfeeding, stress, dehydration, sexual intercourse, sleep and estrogens directly stimulate prolactin synthesis in the pituitary gland. During delivery prolactin also stimulates uterine smooth muscles. Prolactin concentration increases 10-20 times during pregnancy. High prolactin concentration may inhibit function of ovary and testicles, ovulation and FSH and LH secretion.
Prolactine concentration increase could be the only cause of menstrual cycle disorder or total absence of menses. When prolactin concentration is high breast discharge may occur, breast may augment or become sensitive. Prolactin may cause increased sensitivity of the whole body, irritability, depression which are basic symptoms of premenstrual syndrome.
When prolactin blood level is high, pituitary tumor, prolactinoma, could also be suspected. In this case other diagnostic tests should be performed. Prolactin concentration increases in case of metastatic breast cancer. When prolactin concentration decreases mother’s milk is not produced after delivery. Prolactin level decrease in patients with destructive diseases of pituitary gland. Prolactin blood level highly depends on use of medications and narcotic substances.
Increased prolactin level in males inhibits synthesis of testosterone, causes erection disorders, loss of sexual power. Therefore it is very important perform prolactin test in time. Prolactin level should be tested when infertility is suspected, in case of menstrual cycle disorders and erection disorders.
When lactation unrelated with delivery begins, the first necessary test is prolactin level evaluation.
Venous blood is used for test which is performed daily.
Testosterone (TTE)
Testosterone is the principal blood androgen (male sex hormone). In males testosterone is produced in Leydig cells in testicles. LH (luteinizing hormone) stimulates these cells. In females 50% is produced in peripheral tissues, other part of testosterone is produced in ovaries and suprarenal glands. Blood testosterone level in females is 3-4 times lower than in males.
Major part of blood testosterone is bind to sex hormone-binding globulin (SHBG), other part binds with albumin and only 2-3% of blood testosterone is free, and this is its active form.
Testosterone blood level increases after physical activity and decreases when glucose is consumed. In adult males specific daily rhythm predominates: the highest testosterone level observed early in the morning, and in the evening it decreases approximately 25%. Androgen activity is important for the function of genital and other organs. Testosterone is predominant androgen in brain, kidney, it affects production of spermatozoids in testicles and also nitrogen and phosphorus metabolism. After metabolic conversion to dihydrotestosterone, testosterone determinates development of male’s secondary sex characteristics.
Testosterone evaluation is very important in sex glands hypofunction diagnosis. When male genital, organs are underdeveloped (gypogonadism), sperm production disorder occurs and testosterone production decreases. Causes may be congenital (Klinefelter’s syndrome) or acquired (testicle affecting infections, e.g., measles, radiation damage, cytotoxic drugs). Testosterone concentration in males could be decreased due to liver cirrhosis, treatments with estrogens, severe obesity.
Increased testosterone level in females could be due to ovary and suprarenal gland tumors, and anovulation. In females with symptoms of hirsutism (increases hairiness) total testosterone may be normal, yet level of free testosterone may be in creased. In testosterone test level of total blood testosterone is evaluated. In order to evaluate free testosterone, SHBG test should be performed simultaneously.
Venous blood is used for test which is performed daily.
Sex hormone-binding globulin (SHBG)
SHBG is the main transport protein for testosterone. It also bonds to estradiol and dihydrotestosterone.
Increased thyroid function, estrogen excess, treatment with thyroid hormones, anorexia nervosa, pregnancy, liver cirrhosis may increase SHBG blood level. With the increase of years SHBG amount increases. Testosterone level is higher in premenopausal parous woman in comparison with nulliparous. Excess of testosterone and insulin, obesity and polycystic kidney disease may lower level of SHBG.
SHBG evel determination is important for testosterone evaluation. Not bind with SHBG free testosterone is always more active. Status of free androgens could be assessed by calculating free androgen index, FAI, which is calculated by dividing TTE concentration by SHBG concentration and multiplying result by 100. FAI is more sensitive and specific indicator then single changes in TTE and SHBG. FAI increase in case of acne, alopecia, obesity, hirsutism, thyroid hypofunction, polycystic kidney disease. Venous blood is used for test which is performed daily.
Dihydroepiandrosterone sulfate (DHEA-SO4)
DHEA-SO4 is suprarenal gland androgen (male sex hormone). It is inactive, yet it could be metabolized to active androgens. DHEA-SO4 circulates in blood in free form, its level depends on circadian rhythm, and therefore it is excellent marker for androgen secretion in suprarenal glands.
DHEA-SO4 evaluation is important in the assessment of female hairiness (hirsutism), masculinization (male features in female), late maturation and alopecia. When severe acne occurs high serum levels of androgens are often found. Increased concentration of DHEA-SO4 is often observed in patients with polycystic ovaries. DHEA-SO4 test is important for distinguishing hormone-secreting suprarenal gland tumor from ovary tumor (in case of ovary tumor normal levels of DHEA-SO4 are observed).
Venous blood is used for test which is performed daily.
Chorionic gonadothropin (HCG)
HCG is produced by placenta tissue after implantation of fertilized ovum. In the early period of pregnancy it promotes function of yellow body and stimulates synthesis of progesterone (PGN).
Chorionic gonadothropin (HCG) is the basic laboratory test for normal pregnancy. HCG test is performed to diagnose early pregnancy (6-8 days after conception), to determinate pregnancy term and to monitor pregnancy. During pregnancy blood HCG concentration increases very quickly, within first six weeks it doubles every 1-3 days, and reaches its peak (100 000 IU/LN) on approximately 14th week of pregnancy. In normal pregnancy after this HCG level starts to decrease slowly. If HCG level increases further, it could be symptom of the trophoblastic disease (e.g., choriocarcinoma).
In pregnant women with extrauterine pregnancy or threatened abortion HCG and PGN concentration is lowered compared with concentration characteristic for actual term of pregnancy. In marginal cases HCG and PGN test are recommended to perform several times per day in several consecutive days. As HCG is slowly removed from blood, it could be found in blood and urine within 3-6 weeks after abortion.
In order to evaluate fetal risk for malformation HCG, AFP (alfa-fetoprotein) and uE3 (free estriol) levels are evaluated at the second trimester of pregnancy (PRICA-II test).
HCG could serve as tumor marker in the diagnostic and monitoring of germ-cell tumors (testicle and ovary tumors). One of trofoblastic diseases, choriocarcinoma, usually develops from hydatid mole following abortion or normal pregnancy. Although it forms only 1% of all gynecological tumors, it is very important to perform HCG in time, especially evaluation of its free subunit. Venous blood is used for test which is performed daily.