Method for the prevention and treatment of complications gestagenna therapy and contraception

 

(57) Abstract:

The invention relates to medicine. A method for the prevention and treatment of complications gestagenna therapy and contraception, including reception of anti-estrogenic drug. The method normalizes the hormonal status of the woman. 1 C.p. f-crystals.

The invention relates to medicine, more specifically to the gynecologist, and can be used in gynecological clinics and departments of family planning.

Reducing the number of unwanted pregnancies, abortions and sexually transmitted diseases, i.e., the improvement of reproductive and sexual health, is impossible without the use of safe and effective contraception. Millions of healthy women all over the world in the last 30 years using hormonal contraceptives. The most convenient to use are the injectable. Injectable method of contraception used by more than 18 million women in the world. The composition of these contraceptives include progestogen prolonged action - depot medroxyprogesterone acetate (see P. D. Blumental, N. Mcintosh. Quick guide on reproductive health and contraception. - USA, ML, Baltimor: IHPIEGO, 1998.-P. 404).

The medroxyprogesterone predot gatavojamies the endometrium for implantation of the fertilized egg, thicken the cervical mucus, preventing the promotion of sperm. The medroxyprogesterone reduces menstrual pain, reduces the risk of developing benign tumors, cysts, breast cancer, ovarian cancer and endometrial, vasomotor reactions in women at menopause. Prescribe medroxyprogesterone for contraception, as well as in the treatment of endometriosis, fibroids, abnormal menopause. Created numerous pharmaceutical preparations containing as an active start medroxyprogesterone (Depo-provera, provera, Farlutal, MPA and other). Widely used for contraception and treatment and other gestagennye drugs of levonorgestrel, lynestrenol, norethindrone, norgestrela (Auret, Exluton, Micronor and others). These drugs are convenient to use, especially injecting means prolonged action (Depo-provera): 50 mg of the drug is administered 1 time per week, 150 mg for 3 months. However, admission gestagen complications may occur: allergic reactions, thrombosis, insomnia, drowsiness, nervousness, headache, nausea, amenorrhea, menstrual irregularities, depression, weight gain, decreased libido (see Broan R., Clinical pharmacology for midwives-ginekologichna bleeding, not allowing you to use the contraceptive effect of these drugs.

There is a method of prevention and treatment of complications gestagenna therapy and contraception, in particular indiscriminate uterine bleeding, including medication based estrogens, for example, 0.1 mg of ethinyl estradiol in the period from 7 to 21 day menstrual cycle (see I. Manuilov, A. Modern contraceptives. - M.: Medicine, 1983. - S. 79). As a result of taking estrogen uterine bleeding eliminated, but may be the syndrome of estrogen, which is manifested in uterine bleeding or amenorrhea. Disadvantages of treatment with estrogens are also atrophy of the endometrium, the risk of developing breast cancer and endometrial cancer (see Reference Vidal. Drugs in Russia. - M.: Attraversare, 1997.-S. B. 697-8, V. 193).

There is also known a method for the prevention and treatment of complications gestagenna therapy and contraceptives, including combined hormonal preparations on the basis of gestagens and estrogens in 1-2 menstrual cycles (see Robert A. Hatcher and other Guidance on contraception / Russian international edition. - USA, NY: Bridging the Gap Comm., Inc, 1994. - P. 332). Combined marvelon), gestodene (Femoden), levonorgestrel (Ovidon) and others, eliminates complications caused by "pure" estrogen, but simultaneously increases complications gestagenna contraception and therapy, since the concentration of gestagens in the blood increases (see Reproductive health. A guide for physicians / edited by B. M. of Warnica. - K.: CI "Family", 1999. -S. 31).

Known closest to the claimed (prototype) method for the prevention and treatment of complications gestagenna therapy and contraception, including oral nonsteroidal (non-hormonal) anti-inflammatories, such as ibuprofen, 800 mg 3 times a day for 5 days (see guidelines on contraception, Ed. Vovk, I. B., Grassroots N. N. - K.: Blitz-Print.-1998.-S. 80).

Ibuprofen has anti-inflammatory analgesic and mild cough activity. Potency inferior counterparts (indomethacin, ortofen), but better tolerated. Ibuprofen actively prevents and eliminates complications gestagenna therapy and contraception when taken according to a known method in large doses (2400 mg per day). According to modern anti-inflammatory and hemostatic effect of ibuprofen based on the reduction of Pliny proteolytic enzymes. In the mechanism of analgesic action of ibuprofen significant role played by its inhibitory effect on the biosynthesis of prostaglandins (reduces sensitivity to pain nerve receptors). Unlike applied according to the above methods of prevention and treatment of drug action of ibuprofen is not accompanied by characteristic steroid complications (bleeding, amenorrhea, weight gain, depression, etc). However, the disadvantage of this method (prototype) is a contraindication to use it with ulcer disease of stomach and duodenal ulcers, ulcerative colitis, gastritis, enteritis, colitis, hepatitis and cirrhosis of the liver, kidney damage (see Mashkovsky M. D. Medicines. - M.: Medicine, 1993. -T. 1. - C. 214), since the drug has irritant and toxic effects on the tissues of the body.

The basis of the invention is the task in the way of prevention and treatment of complications gestagenna therapy and contraception by short-term use of low doses of nonsteroidal antiestrogen drug to ensure the normalization of the hormonal status of the organism and to start a non-toxic mechanism of complications.

FIPA and contraception, includes the use of nonsteroidal drugs, as a last take an antiestrogen drug 10 mg 1-2 times a day for 2-5 days.

Another distinctive feature of the proposed method is that as an antiestrogen drug use, selected from tamoxifen, and toremifene.

Between the set of features of the invention and achievable technical result there is a causal relationship.

The mechanism of contraceptive action of progestogen is manifested in the thickening of the cervical mucus, preventing sperm penetration; the change of the endometrium, making it difficult to implantation of the eggs; the slow movement of spermatozoa in the fallopian tubes; the suppression of ovulation (an inhibitory effect on the hypothalamic-pituitary system)(see Manual on family planning / Ed. by Vovk I. B., Grassroots N. N. - K.: Blitz-Print, 1998. - S. 75).

The progestogen is effectively used in therapy, for example endometriosis, fibromatous lesions and other endometriosis, in particular luteal phase, increased levels of estradiol and decreased progesterone levels, which creates a favorable background for the development of the endometrium outside its normal localization (see Bori is hodv // Pediatrics, obstetrics genecology. - 1995. - N6. - S. 52). Through estrogenization progesterone nuclear receptors, gestagens in the treatment of their endometriosis increase the level of progesterone in the body and reduce estrogen levels. Uterine fibroids develop in the conditions of reception hyperestrogenemia by reducing the production of progesterone. Therapy progestogen inhibits razrostanie endometrium due to the normalization of hormonal status (see Smrek Century Century Modern, wallenda about poenaru dobreanu pathology of the uterus // Paediatrics, obstetrics and genecology. - 1998. - N3. - S. 99). All gestagens, in addition, regardless of their chemical structure lead to transformation (secretory transformation) proliferative endometrium.

However, in addition to the progesterone receptor, the progestogen may be partially in contact with the glucocorticoid, estrogen, and androgen receptors. This explains the appearance of additional negative effects. The required dose of progestogen depends on the number of progesterone receptors. Therefore, a large number of receptors requires high doses of progestogen. High doses of progestogen due to the antiestrogenic effect reduces the formation of their own receptors. Obviously, it is each menstrual cycle, disordered uterine bleeding, amenorrhea, depression, headache, nausea, insomnia, etc. When discontinuing treatment with progestogen occurs complication is the syndrome of drug - uterine bleeding, amenorrhea.

Because the treatment gestagenna complications with estrogen or combined hormonal preparations containing estrogens and gestagens, creating additional hormonal stress on the female body, bringing new complications and nonsteroidal anti-inflammatory drugs (such as ibuprofen) are caused by pathological changes in the mucous membranes of the gastro-kishechnogo tract, deteriorating liver and kidneys, the goal was to develop an effective method for the prevention and treatment of complications gestagenna therapy and contraception, which would use non-steroidal drugs that do not have negative side effects on the body of the patient.

Since the occurrence of complications gestagenna therapy for contraception is associated in particular with antiestrogenic activity of gestagens, the use of nonsteroidal antiestrogen for the treatment of these complications seems unexpected and illogical unlike izvestnova. - M. : Medicine, 1983. - S. 79). Antiestrogens would strengthen complications gestagenna therapy and contraception. But experience shows the opposite: antiestrogens in a low dose (10 mg 1-2 times a day for 2-5 days) completely, without any unwanted side effects to relieve or prevent complications gestagenna therapy and contraception. The exact mechanism of action of antiestrogens is unknown (see instructions to the drug tamoxifen). Thus, tamoxifen and at least some of its metabolites compete with estradiol for binding to cytoplasmic estrogen receptors in tissues such as the mammary gland, uterus, vagina, anterior pituitary, and tumors containing a high concentration of estrogen receptors. By binding to estrogen receptors antiestrogens prevent the stimulatory effect of estrogen on the synthesis of nucleic acids, which promotes tumor growth restriction. This mechanism has caused cancer antiestrogen in combination with gestagens (see Mashkovsky M. D. Medicines. - M. : Medicine, 1993. - T. 2. - S. 548). Traditionally, long-term use of high doses of antiestrogens. So, toremifene designate up to 240 mg for 1 admission (see ibid., S. 550), and there is repairservice, 1997. - C. C. 152).

Possible short-term effect of low doses of antiestrogens (according to the invention is used 10 mg 1-2 times a day 2-5 days) in the conditions of deficiency of estrogen, which are formed with a long reception of gestagens, has a mild estrogenic effect. Appeared estrogens include a feedback mechanism. Antiestrogenic drugs, by binding to specific receptors that are sensitive to estrogen in the respective carefully selected doses and modes, blocking their action and thus not only change the degree of their biological activity, but also contribute, at least partially, a feedback mechanism, changes in the synthesis and secretion of gonadotropins by adenogipofiza. Thus, the normalization of the hormonal status of the organism, resulting eliminated or prevention of complications gestagenna therapy and contraception without toxic effects on the body. Used drugs are non-steroidal, and therefore does not create additional hormonal stress on the body. In addition, they do not irritate the mucous membranes of the gastrointestinal tract, no toxic effects on the liver and kidneys, due to (1-2 times a day for 2-5 days) are chosen empirically. Lower doses and short term do not have the desired effect on the body, and higher - trigger mechanism, having the opposite of the expected effect on the body. The drugs tamoxifen and toremifene used for the treatment of complications gestagenna therapy in 30 women with endometriosis and fibroids and 30 women - complications gestagenna contraception. Prevention of complications gestagenna contraception and therapy 9 women took tamoxifen and 7 women - toremifene. The treatment was successful and without complications in 74 women. In 2 patients was allergic rash, and the drug is canceled.

The inventive method is as follows.

In case of complications gestagenna therapy and contraceptive use drugs on the basis of medroxyprogesterone acetate, levonorgestrel, lynestrenol, norethindrone, norgestrela as menstrual irregularities, uterine bleeding, headaches, depression, insomnia, etc., the patient is prescribed the pill (taken with water) tamoxifen or toremifene dose of 10 mg 1-2 times a day (morning or morning and evening) for 2-5 days. Prevention of complications gestagenna therapy and contraception reception antiestrogenic t the drug tamoxifen pharmaceutical company Hexal (Germany), Lachema (Czech Republic), Leiras, Finland), Mir Pharmaceutical (USA) and other Drug toremifene - brand name Fareston - produces Finnish company Orion Pharma Int.

Specific examples of the implementation of the proposed method.

Example 1. Patient M., 24 years old, healthy, 1 births and 2 medical abortion. Addressed to the Department of family planning with a request to choose the most suitable method of contraception. The patient M. the recommended injection prolonged gestagennye contraceptive based medroxyprogesterone acetate Depo-provera (Pharmacia decision Upjohn, USA) at a dose of 150 mg 1 every 90 days. 40 days after the first injection, the patient asked the Department of family planning with complaints of bleeding from the uterus. Vaginal studies have shown the norm. Diagnosis: the menstrual cycle in patients receiving gestagennah contraceptive Depo-provera.

Recommended treatment of complications gestagenna of contraception according to the method prototype: the reception of tablets of ibuprofen (moskhimpharmpreparati, Russia) 800 mg 3 times a day for 5 days. After two days of ibuprofen, the patient from treatment was abandoned because of severe pain in the stomach caused by this drug. Then the patient was recommended by the treatment with anti is Uchenie 2 days. Stomach pain and krivomazova stopped after 2 days. In the future, within 2 years, the patient M took the contraceptive Depo-provera (1 injection 150 mg every 90 days) without complications.

Example 2. Patient P., 31, 1 birth, 3 medical abortion. Somatic history is not burdened. Suffer from chronic bilateral adnexitis and the external-internal endometriosis. Addressed to the Department of family planning with a request to choose the most suitable method of treatment and contraception. The patient P. the recommended gestagennye drug Bret (manufactured by Wyeth-Lederle, USA) for contraception and treatment of endometriosis 0,0075 mg 1 time per day at the same time orally in a continuous mode. After 3 months of treatment and contraception patient P. appealed to the Department of family planning with complaints abundant spotting within 14 days and frequent bouts of headaches. Vaginal examination - without pathological changes. Diagnosis: the menstrual cycle - hyperprolinemia taking gestagennah drug Bret, the external-internal endometriosis, chronic bilateral adnexitis in remission. Recommended treatment of complications gestagenna therapy and contraception agree the mg 2 times a day (morning and evening) for 3 days without interrupting the course of the drug, Bret. After a three-day treatment of bleeding and the headaches stopped. The patient P. recommended the admission of avrete for 6 months with subsequent consultation in the Department of family planning. After 6 months of examination of the patient's condition PP showed: spotting and bleeding, headaches did not recur, pregnancy was not, menstrual cycle without violations. According ultrasonic research foci of endometriosis decreased. Feeling normal. The patient P. recommended to continue taking ureta another 6 months.

Example 3. Patient C., 38 years old, childbirth 1, abortions 4, fibroids 6-7 weeks. Somatic history is not burdened. Profuse. Addressed to the Department of planning families about treatment and selection of contraception. The patient Century to contraception and treatment of assigned drug exluton based lynestrenol (firm Organon, Russia). Because of the risk of complications after administration of progestogen in the form of uterine bleeding (reception gestagen + the presence of fibroids), for the prevention of assigned tamoxifen 10 mg 1 time a day for 5 days taken in parallel with eklutna. Receiving exluton patient Century. continued 6 months. Visual inspection of achenium with tamoxifen showed: pregnancy and menstrual cycle was not, the monthly allocation by volume normal, fibromyoma is not increased. The patient Century. recommended to take a progestogen (exluton) another 6 months.

1. Method for the prevention and treatment of complications gestagenna therapy and contraception, including oral non-steroidal drugs, characterized in that as non-steroidal medications take an antiestrogen drug 10 mg 1 - 2 times a day for 2 to 5 days.

2. The method according to p. 1, characterized in that as an antiestrogen drug use, selected from tamoxifen, and toremifene.

 

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