Licensed books on medicine
<< Previous || Next >> |
XXI CENTURY - THE ERA OF NEW ACHIEVEMENTS OF HORMONAL CONTRACEPTION
Hormonal contraception over the nearly 40-year period of its rapid development has established itself not only as one of the most effective methods of preventing an unplanned pregnancy, but also as a new, very promising area of medicine.
A lot of research on this problem, conducted in a number of foreign countries and in our country, has revealed a number of its therapeutic and protective properties, which subsequently led to even greater popularity of hormonal contraceptives among practitioners.
During the period that has passed since the synthesis of the first hormonal contraceptive "Ewed" (1960), a number of new compounds were created with different chemical structures and modes of administration, which were the basis for the creation of new types and forms of hormonal drugs.
The minimum content of the components in tableted oral forms has significantly reduced the number of adverse reactions and practically minimized them. The synthesis of new highly selective progestogens has also determined their higher acceptability.
The development of injection, implantation methods and intrauterine hormonal systems has expanded the possibilities of an individual approach in the appointment of contraception.
Thanks to the achievements in the field of hormone biochemistry, as well as the results of experimental and clinical studies, the qualitative and quantitative composition of hormonal contraceptives has continued to improve and expand to date.
Various combined oral contraceptives as progestogen component contain different compounds and therefore differ from each other in terms of overall metabolic and clinical effects.
A new type of 19-norprogestin used as a progestogen component of COCs is dienogest, which has high selectivity for progesterone receptors, high bioavailability, and a pronounced progestogen effect on the endometrium.
Dienogest (17? -Cyanomethyl-17? -Hydroxy-4,9-estradien-3-on) is a progestin of the 19-nortestosterone group, which has no androgenic effect, and only one of this series of hormones has a 17? -Cyanomethyl group instead of 17 ? -ethynyl group. The antiandrogenic effect of dienogest is especially significant at the cellular level and it is much stronger than that of cyproterone acetate. Dienogest does not bind to SHBG and remains in a free, biologically active state, in a rather high (9%) amount, which provides penetration into the tissue.
The antiandrogenic effect of dienogest is due to the following processes: competitive or non-competitive antagonism to the level of androgen receptors; local suppression of androgen biosynthesis or acceleration of androgen metabolism and excretion; blockade of the enzymatic transformation of testosterone into 5β-dehydrotestosterone (DHT) as a result of the suppression of 5β-reductase; decreased secretion of gonadotropic pituitary hormones, including endogenous testosterone production (Oettel M. et al., 1995).
The great advantage of dienogest in the composition of COCs is its anti-androgenic effect on target cells due to competitive binding to androgen receptors. The therapeutic effect of dienogest was revealed for such symptoms of hyper-androgenia as seborrhea, acne. Thus, in the treatment of patients with symptoms of hyperandrogenism, improvement in patients receiving OK containing dienogest was noted in 87% after 6 months. (Moore, C. etal., 1999).
The effect of OK containing 0.03 mg of ethinyl estradiol and 2 mg of dienogest (Zhanin preparation) on the concentration of sex hormones androgens and globulins that bind sex hormones (SHBG) in healthy young women after three cycles of OK was studied, as well as the antiandrogen effect of this drug was studied. combinations in patients with acne compared with OK containing 0.035 mg of ethinyl estradiol and 2 mg of cyproterone acetate after 6 cycles of therapy. The use of these two combinations of hormonal preparations had a beneficial effect on androgen-dependent skin disorders, mainly acne. The improvement of clinical symptoms was associated with a marked decrease in the concentration of total and free testosterone in the blood serum and a significant increase in the level of SHBG. A moderately pronounced decrease in the level of 5β-dehydrotestosterone and the androgen precursor dehydroepiandrosterone sulfate also has a positive therapeutic effect. Although it is not possible to determine the level of androgens in the hair follicles, a significant decrease in the concentration of androstenediol indicates a suppression of the local formation of 5β-dehydrotestosterone. These results correlate with data from morphological studies: the number of sebaceous glands in the connective tissue decreased significantly. No statistically significant difference in the anti-androgenic properties of the two combinations of hormonal drugs was found.
Dienogest has a pronounced therapeutic effect at a lower dose than other progestins in patients with endometriosis. The effectiveness of treatment with dienogest for pain is 50-90% and does not differ from patients using nafarelin (73-77%), buserelin (72%) and goserelin (70%) (Moore C. et al., 1999).
The gestagen chlormadinone, which is part of Belar's new monophasic combined oral contraceptive (ethinyl estradiol 30 μg and chlormadinone 2 mg), has antiandrogenic properties.
Drospirenone, a new progestogen that is part of the drug Yarin, is very close to endogenous progesterone in its biological properties. Unlike other modern gestagens, it is an analogue of spironolactone. Drospirenone has biological properties similar to those of endogenous progesterone and antimineralocorticoid activity. Drospirenone counteracts the retention of sodium and water caused by aldosterone, which contributes to some side effects of estrogens (including weight gain and breast engorgement). It must be emphasized that the loss of sodium caused by drospirenone is not accompanied by a clinically significant increase in potassium levels. Studies have shown that the drug Yarin due to the antiandrogenic properties of drospirenone has a positive effect on mild and moderate acne in young women.
Other surrogate markers, such as levels of free (unbound) testosterone and SHG G, also indicate favorable changes during therapy with Yarin. It provides excellent control of the menstrual cycle, rarely causing intermenstrual bleeding and amenorrhea. There is convincing evidence that Yarin's contraceptive is effective in treating premenstrual syndrome, and also has a positive effect in general on women's well-being and quality of life associated with health. In addition, the drug Yarina has a beneficial effect on acne and other skin diseases (Foidart J.-M., 2000; Mansour D., 2002). Composition of the drug: 30 μg ethinyl estradiol and 3 mg drospirenone.
A new, extremely interesting type of hormonal contraception is the combined transdermal contraceptive system (ORTO EVRA), which contains 6.0 mg of norelgestromine and 0.75 mg of ethinyl estradiol (EE). The area of its contact with the skin surface is 20 cm2, and about 24 μg of norelgestromine and 20 μg of ethinyl estradiol are released in 24 hours.
Norelgestromin is an active progestogen with practically no androgenic effect. The norelgestromin entering the woman’s body transdermally does not affect the levels of sex hormone-related globulins, and therefore low levels of free testosterone remain that do not differ from normal values (AudetM.C. etal., 2001).
The active ingredients of the transdermal contraceptive system, unlike oral contraceptives, are absorbed through the skin and therefore there is no primary metabolism (in the gastrointestinal tract, liver), which causes a significantly smaller number of adverse reactions.
Large clinical trials (3,300 women) showed that the transdermal system is not inferior to COC in its contraceptive effectiveness. Its effectiveness can only be reduced in women with a body weight of 90 kg (Smallwood G. et al., 2001; Abrams L. et al., 2002; and others).
Thus, women of reproductive age, including teenage girls, can use the transdermal contraceptive system.
Progestin-only oral contraceptives are a reliable alternative to COCs. To date, they are supplemented with another new drug containing 75 micrograms of desogestrel (Charozetta, Organon, Netherlands).
The main goal in developing the Charozet drug was to produce an oral contraceptive that did not contain an estrogen component, but which could permanently block ovulation in the same way as COCs, and therefore its contraceptive reliability was comparable to COCs. Charozetta has a high selectivity for progesterone receptors, low androgenic activity, and therefore will cause fewer adverse reactions.
In a double-blind comparative study of the effectiveness of 75 mcg / day of desogestrel and 30 mcg / day of levonorgestrel (Rice et al., 1999), a higher contraceptive effectiveness of desogestrel was found (the Pearl index was 0.14 for desogestrel and 1.17 for left, respectively nor-gestral). For comparison, it should be said that the Pearl index for low-dose COCs varies from 0.12 to 0.5 (Trussell et al., 1987); for traditional progestin-containing contraceptives, the Pearl index is 0.5–3.0 (McCann, Potter, 1994). Therefore, the contraceptive reliability of Charozetta is similar to COC.
In 1991, a new NovaRing contraceptive ring was designed, tested through numerous clinical studies, and subsequently introduced into clinical practice.
NovaRing is a flexible, transparent ring made of evatan (ethinyl vinyl acetate), 54 mm in diameter and 4 mm thick in cross section. Each ring contains 2.7 mg of ethinyl estradiol and 11.78 mg of etonogestrel. According to the biological gradient, by diffusion from the ring into the vagina, 15 μg of ethinyl estradiol and 120 μg of ethonogestrel are released daily. The combination of these hormones provides the level of steroid hormones in the blood, optimal for achieving a contraceptive effect. The maximum concentration of hormones in blood plasma is reached a few days after the introduction of NovaRing, and due to the constant continuous release of hormones from the membrane of the ring, there are no differences in their concentration in blood plasma.
According to the daily release of the estrogen component (15 mcgetinylestradiol), NovaRing corresponds to ultramicrocosed oral contraceptives.
Each ring is intended for use during 1 menstrual cycle, including 3 weeks. its application and 1 week. a break. An important advantage is that the ring is easily inserted and removed by the woman herself, while the elasticity and softness of the ring allows both the woman and the partner not to experience any unpleasant sensations.
The contraceptive mechanism of NovaRing is due to the suppression of ovulation and an increase in the viscosity of cervical mucus. It has been found that NovaRing suppresses ovulation as effectively as combined oral contraceptives.
The results of clinical trials conducted from 1997 to 1999. confirmed not only the high contraceptive effectiveness and acceptability of NovaRing, but also good cycle control during contraception, the absence of a negative effect on hemostasis, blood lipid spectrum, blood pressure, body weight. Implanone is a new contraceptive implant (1 capsule for subcutaneous administration), contains etonogestrel, which is an active metabolite of desogestrel and has a high selective activity to progesterone receptors and minimal androgenic effect. The introduction of the implant is less traumatic compared to the norplant (5 capsules). The contraceptive effect persists for 3 years. After removal of the implant, a rapid restoration of fertility is observed (Urbancsel J., 1998; Bennink H., 2000).
| << Previous || Next >> |
| = Skip to textbook content = |
XXI CENTURY - THE ERA OF NEW ACHIEVEMENTS OF HORMONAL CONTRACEPTION
- Physical development of socially different populations of children and adolescents living in various territories of Russia in the first decade of the 21st century
In the previous paragraph, the hygienic characteristics of the studied populations of children and adolescents were given and their social differences were shown. Since physical development is considered as an indicator of the sanitary-epidemiological well-being of the population, it can be assumed that it will have differences in these populations. For the description and analysis of indicators of physical development were selected
- HORMONAL CONTRACEPTION
Currently, the most effective method for preventing unwanted pregnancy is hormonal contraception (HA), based on the use of synthetic analogues of female sex hormones. Depending on the composition and method of administration, modern hormonal contraceptives are divided into groups shown in table 2.2. Hormonal contraception refers to
- Hygienic characteristics of socially different populations of children and adolescents living in various territories of Russia in the first decade of the 21st century
The study was performed by the method of natural hygienic experiment using methods of epidemiological studies. The following populations of children and adolescents were studied: 1. Children living in the conditions of a Moscow metropolis and studying in 11 general educational institutions (longitudinal monitoring). 2. Children and adolescents - social orphans, pupils of state
- Hormonal contraception
Hormonal contraception is currently the most common method for preventing unwanted pregnancy. And although more than forty years of intensive research has been conducted on this problem (since the development of the first contraceptive drug Enovid - “Pincus tablets” in 1959 by the American physiologist G. Pincus together with obstetrician-gynecologists), dozens of hormonal
- HORMONAL CONTRACEPTION
To date, in our country, the main means of birth control is still an artificial abortion, which causes great harm to women's health. It is difficult to comprehensively assess the negative consequences of abortion. The range of detrimental consequences of artificial abortion is quite large and includes both immediate ones (traumatic complications, bleeding, menstrual irregularities, inflammatory
- Hormonal oral contraception
Contraception using combined oral agents. Currently, contraception using combined means (COCs) is one of the most common. The composition of COCs includes synthetic estrogenic and progestogen compounds, due to the action of which pregnancy is protected. The first drugs were synthesized in the late 50s (Eidan - "Pincus tablets") and
- MAN HORMONAL CONTRACEPTION
In recent years, the possibility of wider participation of men in family planning has been discussed. In addition to the use of condoms, periodic abstinence, and the method of interrupted sexual intercourse, it is expected that male hormonal contraception (MGC) will be used in the very near future. The basic principles of using hormonal male contraception are as follows:
- Hormonal contraception - general information
The first oral contraceptives appeared at the turn of the 50s - 60s. this century. The first oral contraceptive Enovid (1959) contained 0.15 mg of mestranol and 10 mg of norethinodrel. Subsequently, the method of hormonal contraception underwent significant improvements, among which it is necessary to distinguish the following: • firstly, in combined OK doses of hormones significantly decreased with
- HISTORY OF HORMONAL CONTRACEPTION DEVELOPMENT
The creation of hormonal contraception was a new milestone in the prevention of pregnancy. Even in the second half of the last century, it was noted that during pregnancy follicular maturation ceases, that is, during this period, repeated pregnancy becomes impossible. Based on this, Ludwig Haberbladt in the early years of our century proved in experiment that extract of the corpus luteum
- GENERAL INFORMATION ON HORMONAL CONTRACEPTION
The creation of hormonal contraception was a new milestone in the prevention of pregnancy. The discovery of sex hormones (in 1929 - estrogen, and then - progesterone, synthesized in 1934 by Gutenaht) was the first stage in the development of contraception. Gutenacht proved the blocking effect of progesterone on the ovulation process. Following this, a large number of reports of physiological properties
- Hormonal contraception
- NON-HORMONAL METHODS OF CONTRACEPTION Intrauterine contraception
Inside, uterine contraception (IUD) is one of the most common effective methods for preventing unwanted pregnancy. According to the WHO, currently more than 60 million women use various types of intrauterine devices (IUDs), which are second only to oral hormonal contraceptives in popularity. In Russia, according to statistics, this method