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Female sexual hormones


female-sexual-hormones

Female sexual hormones are the basis of the sexual function of women. They influence the growth and development of female sexual organs, secondary sexual characteristics, reproduction, forming of the osseous system and complex behavior. They are mostly secreted in the ovaries. After the ovulation, follicle is filled with blood (corpus rubrum), and with surrounding cells, it makes the yellow body (corpus luteum) which persists to the next menstruation, or in case of pregnancy, secretes estrogens and progesterone, together with the placenta. Estrogens and gestagens belong to the group of steroidal hormones which means that they are received from cholesterol and they work through the intracellular receptors.

The secretion of estrogen and progestagen is under control of gonadothropin which is created by the hypophysis by the regulation from the hypothalamus (GnRH), hormone which releases gonadothropins.

Gonadothropins are secreted in the hypophysis (FSH and LH) and in the placenta (HCG). The secretion of LH and FSH is regulated by GnRH which is created in the hypothalamus. FSH is a hormone which stimulates the follicles of the ovaries and secretion of estradiol. LH stimulates the interstitial cells of the ovaries and secretion of progesterone in the yellow body. HCG is similar to LH, chemically and functionally, and it is created by the placenta. PIH (prolactin inhibiting hormone) is also created in the hypothalamus, and it slows down the secretion of prolactin.

Estrogen

Three major estrogens are estradiol, estran and estranol. They work by receptors in the uterus, vagina and breast, as well as hypothalamus and hypophysis, liver, kidneys and heart. They stimulate the creation of progesterone receptors. During puberty, they influence the development of sexual organs and sexual secondary characteristics. They influence the proliferation of endometrium during the reproductive period. They have a bit of mineral-corticoidal effect, so in the second phase of menstrual cycle, they cause the retention of water and salt. They have a positive effect on the medulla by prevention of absorption. They reduce the concentration of HDL in plasma, and in higher dosage, they prevent ovulation in women, and in men, with higher concentrations, they cause the stoppage of spermatogenesis and atrophia of the testicles.

They are used in primary hypogonadism as hormonal contraception, the therapy in menopause, atrophic vaginitis and prostate cancer. Due to solubility in lipids, they can be applied per os, intramusculary, transdermally or vaginally.
Side effects are hyperplasia of the endometrium, sickness, vomiting, edema, tension of breasts, disorder of the liver function, increased risk of thromboembolism. In pregnancy, they should not be taken because they cause malformations of the fetus, and also increased risk of carcinoma.

Apart from natural estrogens, today, there are numerous synthetic compounds which have an estrogenic effect. Those are ethynilestradiol, mestranol, quinestrol, diethylstilbestrol.

Progestagens

Those are steroidal sexual hormones which have a similar effect to progesterone. Natural progesterone is rarely used in clinical practice today. Progesterone itself has additional estrogenic, androgenic, anabolic and corticosteroidal effect. Those are: norgestrel, gestoden, norgestimat, noretisteron, dienogest, norelgestromin, drospirenon, medroxiprogesteron, didrogesteron, tibolon, megestrol, etc.

They are used in different states when additional effect is necessary, but mostly in the hormonal therapy in menopause and as a progestagenic component of oral contraceptives.

At the beginning of menopause, in a woman, there is a smaller number of sexual hormones and their concentration in the body is reduced, which causes numerous changes in the body. The treatment with hormones removes difficulties such as vasomotor (heat, sweating, changes of mood, atrophic vaginitis), reduces the risk of circulatory diseases, etc.
There are two types of preparations: sequential preparations used during 25 days, progestagen in the last 10-13 days of the therapy by estrogen, after which there is a 5-6 day break when bleeding starts. Another way is continuous intake of estrogen, and progestagen is added in the first 10-13 days every month. The introduction of progestagen reduces hyperplasia of endometrium, caused by estrogens, and the risk of carcinoma of endometrium.
Side effects are higher risk of breast cancer and endometrial cancer.

Progesterone

It is secreted in the yellow body of the ovaries after ovulation. Endometrium is changed in order to become ready for the implantation of the fertilized egg. In case of pregnancy, trophoblast secretes gonadothropin which supports the function of the yellow body, and during the third month of pregnancy, the placenta starts secreting large amounts of estrogen and progesterone, so the yellow body loses its function. It is used in the preparations for oral contraception or hormonal therapy in menopause, as well as in the treatment of metrorrhagia, dysmenorrhea or endometriosis. A great problem of substitution postmenopausal therapy is that there are hypertension and higher risk of development of uterus cancer and breast cancer.

Progesterone is necessary for the regular maintainance of pregnancy. In case of the drop of the necessary concentration of progesterone, there is miscarriage. In pregnancy, gestagenic preparations are used during the first trimester for the prevention of miscarriage.

Didrogesterone

It is an oral progestagen which has a pure progesterone effect without androgenic, estrogenic, termogenic, corticosteroidal or anabolic effects. It can stimulate the secretion phase of endometrium regardless of estrogen. It is used in the treatment of all gynecological disorders where it is necessary to apply gestagenes, and those are hormonal therapy in combination with estrogens, physiological postmenopause or the state after ovariectomy, disorders of the menstrual cycle such as irregular cycles due to hormonal disbalance, dysfunctional uterine bleeding, dismenorrhea, secondary amenorrhea, menometrorrhagia without organic cause. It is also applied in premenstrual syndrome, infertility due to the yellow body failure, in habitual miscarriage.

It must not be applied in cases of vaginal bleeding of unknown origin, heavy liver disorders, icterus in pregnancy, Dubin-Johnson’s syndrome, Rotor’s syndrome, in case of tumor dependent of progesterone in anamnesis.
It can lead to the retention of liquid, so it should be carefully applied to patients with heart diseases, blood vessel and renal diseases, diabetes, asthma, epilepsy, migraine or other states which could get worse by the retention of liquid.

Side effects occur rarely and they do not require the interruption of treatment. Rare bleeding in the middle of menstrual cycle stops with the increase of the dosage. Rarely, it can come to the loss of appetite, sickness, tension in the chest, headache, dizziness and the feeling of flatulence. There is sometimes migraine, depression, change of libido, change of values of the liver function and jaundice.

Combination of estrogen and progesterone

Such combinations are very often used because of the substitution therapy. They contain both estrogen and progesterone. They are safer for the clinical use than progestagenes, and they aim at imitating of the normal hormonal conditions in women in menopause. Sequential preparations are more adequate, because by changing of the concentrations of estrogens and progestatene, the functions of ovaries are completely simulated.

Registered drugs:

  • estradiol – VAGIFEM (Novo Nordisk Denmark ), CLIMARA (Schering Germany), ESTRADERM TTS (Novartis Switzerland), ESTROFEM (Novo Nordisk Denmark), OESTRADIOL (Galenics Serbia),
  • estriol – OVESTIN (Organon Netherlands),
  • hidroxiprogesterone - PROGESTERON DEPO (Galenics Serbia),
  • progesterone – CRINONE (Fleet Laboratories Limited Great Britain),
  • didrogesterone – DABROSTON (Belupo Croatia),
  • noretisteron – PRIMOLUT-NOR-5 (Schering Germany),
  • linestrenol – ORGAMETRIL (Organon Netherlands),
  • tibolon – LIVIAL (N.V.Organon Netherlands),
  • estradiol valeat, norgestrel - CYCLO-PROGYNOVA (Schering Germany),
  • estradiol, noretisteron – ACTIVELLE (Novo Nordisk Denmark), KLIOGEST (Novo Nordisk Denmark), TRISEQUENS (Novo Nordisk Denmark),  
  • drospirenone, estradiol – ANGELIQ  (Schering Germany),
  • progesterone, estradiol – LUTESTROL (Galenics Serbia),
  • dienogest, estradiol – KLIMODIEN (Schering Germany),
  • dienogest, etinilestradiol – JEANINE (Schering Germany),


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