Gonadotrophins are human hormones produced by the anterior pituitary gland. The gonadotrophins include: follicle stimulating hormone - FSH and luteinizing hormone - LH. What is the norm of gonadotrophins? What are the effects of excess or deficiency in gonadotropins?
Gonadotrophins - role
Gonadotrophins , as the name suggests, are designed to stimulate the activity of human gonads (ovaries and testes). They are necessary for proper procreation.
Gonadotropins, or follitropin and lutropin, consist of two α and β subunits, but only the beta chain determines biological activity. Their secretion is stimulated by gonadoliberin (GnRH) secreted by the hypothalamus. Low frequency of pulsations stimulates FSH secretion and high LH secretion.
The regulation of the hypothalamic-pituitary-ovary axis occurs through three types of feedback loops:
- long loop - feedback between the hormonal function of the ovaries and the function of the hypothalamus and pituitary gland
- short loop - feedback between the hormonal activity of the pituitary gland and the hypothalamus
- ultra-short loop - changes in the concentration of the releasing hormone within the cell
FSH attaches in the ovary to receptors on the surface of the granulosa cells that surround the dominant follicle in the ovary. They have the ability to aromatize androgens into estrogens when stimulated by FSH and, together with estrogens, stimulate the appearance of LH receptors.
During the follicular phase of the menstrual cycle, follitropin stimulates the maturation of the dominant follicle, which in turn secretes estradiol and inhibin, and inhibits FSH secretion (negative feedback).
When estradiol levels increase appropriately within 48 hours, the hypothalamus releases a large amount of GnRH and there is a peak of FSH and LH (positive feedback) secretion, which results in ovulation - that is, the dominant follicle ruptures and the egg is released. FSH levels remain low throughout the rest of the cycle to prevent more eggs from maturing in the ovary.
In men, FSH has receptors on Sertoli cells, causes enlargement of the seminal tubules, together with testosterone stimulates spermatogenesis (sperm production) and increases the production of androgen binding protein, necessary for propertestosterone functioning.
During the menopause, due to the extinction of the hormonal activity of the gonads, both women and men have increased levels of FSH in the blood and thus in the urine.
Theecal cells, which also surround the dominant follicle, have a lutropin receptor and the ability to produce androgens from cholesterol. LH initiates further division of the ovum and the process of luteinization (transformation of granular cells into lutein cells of the corpus luteum) and the production of an increased amount of progesterone.
The release of progesterone depends on the LH pulses, it occurs by the lutein cells in the corpus luteum, which arose after ovulation at the site of the dominant follicle from which the egg was released. Progesterone secretion peaks at 8–9. the day after ovulation. Under its influence, there is a further increase in the thickness of the endometrium in the uterus.
When fertilization is not achieved, usually 14 days after ovulation in the corpus luteum, progesterone production ceases, its regression begins and it changes into a non-vascular scar, and the endometrium in the uterus peels off in the form of monthly bleeding.
In women who have fertilized and implanted the embryo, the function of the corpus luteum is supported by human chorionic gonadotropin - the aim is to maintain the production of progestreone.
In men, LH stimulates testosterone production by acting on Leydig cells in the testes.
Correct Gonadotropin Level
The level of FSH and LH in women depends on the day of the menstrual cycle and age. It shows daily variability with the maximum in the morning. In children, FSH levels - except in the period right after birth, when FSH spikes are observed - are low and increase before puberty.
Correct concentration of gonadotropins in women
1) FSH: in the follicular phase 1.4-8.6 IU / l, during ovulation 2.3-21 IU / l, postmenopausal 42-188 IU / l
2) LH: in the follicular phase 0.2-26 IU / l, during ovulation 25-57 IU / l, postmenopausal 8-102 IU / l
Gonadotropin deficiency
LH and FSH deficiency not only leads to fertility disorders, but also to amenorrhea, erectile dysfunction, libido and the absence of tertiary sexual characteristics (sexual hair).
A medical condition with reduced FSH and LH levels as a result of dysfunction of the hypothalamus or pituitary gland is called hypogonadotrophic hypogonadism. Secondly, this leads to an estrogen deficiency. Depending on the age at which gonadotropin deficiencies occur, we can observe different clinical symptoms before and after sexual maturation.
Symptoms of hypogonadism before puberty:
- in boys - delayed sexual maturation (underdevelopment of external genitalia, no mutation, gynecomastia), eunuchoid body structure (tall, long limbs, gynecoid fat breakdown)
- in girls - primary amenorrhea, underdevelopment of external and internal genitalia, underdevelopment of the nipples
After puberty: in men - reduction of pubic, axillary and facial hair, reduction of muscle strength and mass, osteoporosis, atrophic spermatogenesis, reduction of ejaculate volume, in women - secondary amenorrhea (anovulation), hair loss armpit, atrophy of the vulva and vagina.
Common causes of decreased gonadotropin levels
- hypothalamic diseases - tumors (craniopharyngioma, glioblastoma, meningioma, neoplastic metastases), infiltrative and inflammatory diseases (sarcoidosis, tuberculosis, syphilis, mycosis, leukemic infiltrates), injuries, vascular defects (aneurysms, hemorrhagic strokes and ischemic strokes) , radiotherapy, malnutrition, drugs, genetic diseases (Kallmann syndrome, Prader-Willie syndrome, Laurence-Moon-Biedl syndrome, Morsier syndrome)
- pituitary diseases - tumors (pituitary adenoma, adenoma, cysts, craniopharyngioma, meningioma, glioma, neoplastic metastases), infiltrative and inflammatory diseases (sarcoidosis, hemochromatosis, encephalitis or meningitis, lymphocytic inflammation), postpartum ischemic stroke (from Sheehan), necrosis in diabetes mellitus, trauma with detachment of the stalk, intraoperative damage to the stalk or pituitary gland, congenital absence of the pituitary gland, vascular defects (aneurysms, pituitary infarction), radiotherapy, malnutrition, drugs, empty saddle syndrome.
Elevated levels of gonadotrophins
Increased levels of FSH and LH in the absence or decreased secretion of steroid hormones by the gonads (ovaries and testes) and at the same time the absence or decreased fertility is called hypergonadotrophic hypogonadism.
The most common reasons for it:
- congenital hypothyroidism: congenital absence of testicles (torsion in utero), testicular dysgenesis (X0, X / XY, XY, XX), Klinefelter syndrome (47, XXY), bilateral cryptorchidism, atrophic testes syndrome
- acquired testicular hypothyroidism: hemochromatosis, acquired testicular atrophy (injuries, inflammation, testicular torsion), radiation and chemotherapy, pharmacological castration (testicular cancer)
- aging male reproductive system
- congenital damage to the ovaries: gonadal agenesis, genetic diseases - Turner syndrome 45, X0, gonadal dysgenesis (45, X; 46, XX; 47, XXX), cleargonadal dysgenesis
- acquired ovarian damage: sarcoidosis, radiation therapy, chemotherapy, surgical removal, autoimmune hypoplasia
- premature ovarian failure syndrome
Disturbances in the proportion of gonadotropin secretion
We can also distinguish the state of disturbed proportion of gonadotropin secretion:
- increased stimulation of FSH secretion than LH occurs in anorexia nervosa and in certain disorders of the hypothalamus (the so-called pre-pubertal type of response)
- Overexcitation, mainly LH secretion, is seen in polycystic ovary syndrome (PCOS)
The concentration of FSH may be influenced by taking medications - contraceptives, some hormones and drugs (phenothiazines reduce its concentration, while levodopa, cardiac glycosides, clomiphene increase its concentration)
Diagnosis of gonadotropin deficiency
The diagnosis of FSH and LH deficiency consists in assessing the concentration of these hormones in the blood and performing functional tests. It is a test to stimulate the secretion of gonadotrophins after administration of gonadoliberin (GnRH). The purpose of the test is to assess the efficiency of the hypothalamic-pituitary-gonadal axis.
It is used in the diagnosis of hypogonadotrophic hypogonadism, as well as in the diagnosis of pubertal disorders.
Another indication for the test is the assessment of the pituitary reserve. GnRH is administered intravenously. The concentration of gonadotropins: LH, FSH is determined at three time points - before drug administration (time point 0), at 30 and 60 minutes of the test.
In menstruating women, the test is performed in the follicular phase of the cycle or after bleeding is induced with a progestogenic preparation. Normal stimulation of gonadotropin secretion is a 3-8-fold increase in LH concentration with a peak at 30 minutes and a 3-4-fold increase in FSH concentration with a peak at 60 minutes.
No answer is found when the pituitary gland is missing or damaged. A weakened response indicates a disturbance in the functions of the hypothalamic-pituitary system or may occur after treatment of pituitary tumors (surgery, radiation).
FSH assessment is also needed to assess the so-called ovarian reserve - this is the number of follicles in the ovary that are capable of growth and development of the egg. Every woman is born with a certain ovarian reserve, which decreases irreversibly over the course of life.
The most appropriate ovarian reserve test is FSH and estradiol or AMH.
A reduced ovarian reserve result does not necessarily mean that you are unable to become pregnant and should not be used solely as a basis forto limit or refuse infertility treatment.
In order to assess the ovarian reserve, a test with clomiphene citrate is performed. In women with normal FSH levels, on day 3 of the cycle, 100 mg of clomiphene citrate is administered orally for 5 days, between day 5 and day 9 of the cycle. Blood FSH levels are measured on days 3 and 10 of the cycle. If both test concentrations are 10 IU / L and day 10<10 IU/l to wynik jest nieprawidłowy i świadczy o małej rezerwie jajnikowej.
Changes in the hypothalamus and pituitary gland are imaged using CT or MR with contrast.
Indications for the gonadotropin concentration test
The indications for the FSH concentration test are diagnostics:
- infertility in women and men
- menstrual disorders
- diseases of the pituitary gland
- ovarian diseases
- a small amount of sperm in the semen (oligospermia)
- testicular diseases
- abnormal puberty in children (premature, delayed)
- premature menopause
Treatment of gonadotropin secretion disorders
The treatment of gonadotropin secretion disorders depends on its cause. substitution of exogenous gonadotropins, substitution of sex steroids.