The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform
Donna Mctavish - One of the best experts on this subject based on the ideXlab platform.
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Transdermal Estradiol/Norethisterone
Drugs & Aging, 1994Co-Authors: Lynda R Wiseman, Donna MctavishAbstract:Synopsis The combined transdermal estradiol/Norethisterone therapeutic system is designed to deliver both estradiol and Norethisterone into the systemic circulation at a constant rate for up to 4 days when affixed to the skin. Transdermal administration avoids hepatic first- pass metabolism, allowing therapeutic concentrations of the progestogen and estrogen to be maintained in postmenopausal women following low dose administration. Transdermal Norethisterone does not appear to alter the potentially beneficial effects of transdermal estradiol on total cholesterol low- density lipoprotein (LDL) or triglyceride levels, or metabolic parameters of bone resorption or vaginal cytology. Protection of the endometriumfrom the effects of unopposed estradiol is achieved by sequential treatment with transdermal estradiol/Norethisterone for 2 weeks of each 28- day cycle, and the majority of patients experience a regular vaginal bleeding pattern with this treatment regimen. Menopausal symptoms are improved to a similar extent during the transdermal estradiol- only and combined estradiol/Norethisterone treatment phases. The transdermal therapeutic system has been well accepted by patients in clinical trials. It is generally well tolerated, the most common adverse effect being local irritation at the site of application. Estrogen- and progestogen- related systemic adverse events are reported in a small proportion of patients. Thus, the combined estradiol/Norethisterone transdermal delivery system offers a more convenient and consistent method of progestogen administration. Together with its therapeutic efficacy when administered at lower dosages than oral therapy, it is likely to further improve patient compliance during hormone replacement therapy. Pharmacological Properties The combined estradiol/Norethisterone therapeutic system is designed to deliver 0.05 mg/day estradiol and 0.25 mg/day Norethisterone (given as the acetate) at a constant rate for up to 4 days. Following application of the delivery system to intact skin, steady-state plasma concentrations of Norethisterone (the active gestogen), were between 1.6 and 3.2 nmol/L 2 days after the first application. Steady-state concentrations of estradiol of 0.15 to 0.18 nmol/L were reached within 24 hours, and were similar to estradiol levels in the early follicular stage of the ovulatory cycle in premenopausal women. Estradiol is rapidly cleared from the circulation following transdermal administration, with a plasma elimination half-life (t_½) of about 1 hour. The t_½ of Norethisterone varies between 6 and 8 hours. Metabolism of both estradiol and Norethisterone occurs mainly in the liver, the major metabolites being estrone, estriol and their conjugates, and the 5β,3α-Norethisterone Derivative, respectively. Metabolites are mainly excreted as sulphate and glucuronide conjugates in the urine, although some enterohepatic recirculation may occur. Plasma concentrations of estradiol and Norethisterone return to pretreatment values within 24 and 48 hours of patch removal, respectively. Transdermal estradiol therapy appears to have a positive effect on cardiovascular disease risk factors in postmenopausal women, which may be mediated in part by the beneficial changes in lipid and lipoprotein profiles observed in patients receiving transdermal estradiol for ≥ 3 months. Addition of sequential transdermal Norethisterone does not appear to significantly affect the reduced plasma levels of total and low density lipoprotein (LDL) cholesterol induced by estradiol, and triglyceride levels are reduced by a similar extent during both the estrogen-only and combined estrogen/Norethisterone treatment phases. Transdermal estradiol appears to have a favourable effect on carbohydrate metabolism and no net adverse effect is observed following coadministration of transdermal Norethisterone. The effects of combined transdermal estradiol/Norethisterone on haemostatic factors and arterial status have yet to be determined. During transdermal estradiol/Norethisterone therapy, vaginal cytology is converted to a pattern similar to that found in premenopausal women, with increased numbers of superficial and decreased numbers of basal and parabasal cells. Transdermal estradiol inhibits bone resorption, as evidenced by a reduction in the urinary ratios of calcium and hydroxyproline to creatinine, and stabilisation of, or small increases in, bone mineral density in postmenopausal women receiving long term treatment. Concomitant progestogen therapy does not appear to impair, and may enhance, the bone conserving effects of estrogens; however, further investigation is necessary to confirm the latter findings. Clinical Use The clinical efficacy of the combined transdermal estradiol/Norethisterone delivery system in preventing endometrial hyperplasia and controlling climacteric symptoms has been investigated in noncomparative clinical trials of up to 3 years’ duration. In most studies, transdermal estradiol 0.05 mg/day was administered for the first 2 weeks of a 28-day cycle, followed by combined transdermal estradiol/Norethisterone 0.05/0.25 mg/day for the last 2 weeks. The combined transdermal estradiol/Norethisterone delivery system provided endometrial protection from unopposed estradiol. Biopsy samples from more than 400 treated women showed proliferative endometrium in 1.5 to 7% and secretory endometrium in 57 to 100%. The incidence of hyperplasia in women receiving this treatment regimen was less than 2%. Sequential transdermal Norethisterone induced a regular vaginal bleeding pattern in about 80% of women. Regular bleeding episodes occurred in 80 to 90% of cycles, with irregular episodes in about 5 to 11%. Amenorrhoea occurred in about 6 to 9% of cycles during therapy. In 2 small studies in which 30 women received continuous transdermal estradiol/Norethisterone, the incidence of amenorrhoea was 53 and 100% after 6 months. Climacteric symptoms including hot flushes, sweating, sleep disturbance, vaginal discomfort, poor concentration and irritability were significantly improved compared with baseline in patients receiving transdermal estradiol with sequential transdermal Norethisterone. Tolerability The most frequently reported adverse effects in women using transdermal estradiol or combined transdermal estradiol/Norethisterone delivery systems are dermatological reactions. Transient mild erythema and itching at the site of application are the most common events. However, severe cutaneous irritation necessitating withdrawal of treatment is experienced by about 6% of patients using the estradiol-only or combined delivery systems. The occurrence of skin reactions can be minimised by selection of new sites when applying patches. Adverse systemic events associated with estrogen or progestogen therapy occurred in a small proportion of women and included breast tenderness, vaginal spotting or bleeding, fluid retention, headache, nausea, gastrointestinal disturbances, bodyweight gain and depression. Of these events, unacceptable vaginal bleeding was the most common reason for patients discontinuing combined estradiol/Norethisterone therapy (affecting 6 to 10%). Transdermal estradiol did not stimulate hepatic metabolism and therefore no increases in plasma levels of renin substrate, sex hormone-, thyroxin-, and cortisol-binding globulins or clotting factors were observed; however, a slight decrease in sex hormone-binding globulins was observed during combined transdermal estradiol/Norethisterone treatment. Dosage and Administration For treatment of postmenopausal symptoms and symptoms of estrogen deficiency due to surgical menopause, and for prevention of postmenopausal osteoporosis in women with an intact uterus, transdermal estradiol 0.05 mg/day is recommended for the first 14 days of a 28-day cycle, followed by 14 days of combined transdermal estradiol 0.05/Norethisterone 0.25 mg/day. The transdermal delivery system should be applied to clean dry intact skin and should be changed twice weekly. Contraindications to the use of estradiol include carcinoma of the breast or endometrium, vaginal bleeding of unknown origin, previous estrogen-associated, or active thromboembolic disease or thrombophlebitis. Caution is advised in patients with past or present endometriosis, uterine leiomyomata, impaired hepatic or renal function, conditions likely to be influenced by fluid retention, or a history of depression or pregnancy-associated jaundice.
Lynda R Wiseman - One of the best experts on this subject based on the ideXlab platform.
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Transdermal Estradiol/Norethisterone
Drugs & Aging, 1994Co-Authors: Lynda R Wiseman, Donna MctavishAbstract:Synopsis The combined transdermal estradiol/Norethisterone therapeutic system is designed to deliver both estradiol and Norethisterone into the systemic circulation at a constant rate for up to 4 days when affixed to the skin. Transdermal administration avoids hepatic first- pass metabolism, allowing therapeutic concentrations of the progestogen and estrogen to be maintained in postmenopausal women following low dose administration. Transdermal Norethisterone does not appear to alter the potentially beneficial effects of transdermal estradiol on total cholesterol low- density lipoprotein (LDL) or triglyceride levels, or metabolic parameters of bone resorption or vaginal cytology. Protection of the endometriumfrom the effects of unopposed estradiol is achieved by sequential treatment with transdermal estradiol/Norethisterone for 2 weeks of each 28- day cycle, and the majority of patients experience a regular vaginal bleeding pattern with this treatment regimen. Menopausal symptoms are improved to a similar extent during the transdermal estradiol- only and combined estradiol/Norethisterone treatment phases. The transdermal therapeutic system has been well accepted by patients in clinical trials. It is generally well tolerated, the most common adverse effect being local irritation at the site of application. Estrogen- and progestogen- related systemic adverse events are reported in a small proportion of patients. Thus, the combined estradiol/Norethisterone transdermal delivery system offers a more convenient and consistent method of progestogen administration. Together with its therapeutic efficacy when administered at lower dosages than oral therapy, it is likely to further improve patient compliance during hormone replacement therapy. Pharmacological Properties The combined estradiol/Norethisterone therapeutic system is designed to deliver 0.05 mg/day estradiol and 0.25 mg/day Norethisterone (given as the acetate) at a constant rate for up to 4 days. Following application of the delivery system to intact skin, steady-state plasma concentrations of Norethisterone (the active gestogen), were between 1.6 and 3.2 nmol/L 2 days after the first application. Steady-state concentrations of estradiol of 0.15 to 0.18 nmol/L were reached within 24 hours, and were similar to estradiol levels in the early follicular stage of the ovulatory cycle in premenopausal women. Estradiol is rapidly cleared from the circulation following transdermal administration, with a plasma elimination half-life (t_½) of about 1 hour. The t_½ of Norethisterone varies between 6 and 8 hours. Metabolism of both estradiol and Norethisterone occurs mainly in the liver, the major metabolites being estrone, estriol and their conjugates, and the 5β,3α-Norethisterone Derivative, respectively. Metabolites are mainly excreted as sulphate and glucuronide conjugates in the urine, although some enterohepatic recirculation may occur. Plasma concentrations of estradiol and Norethisterone return to pretreatment values within 24 and 48 hours of patch removal, respectively. Transdermal estradiol therapy appears to have a positive effect on cardiovascular disease risk factors in postmenopausal women, which may be mediated in part by the beneficial changes in lipid and lipoprotein profiles observed in patients receiving transdermal estradiol for ≥ 3 months. Addition of sequential transdermal Norethisterone does not appear to significantly affect the reduced plasma levels of total and low density lipoprotein (LDL) cholesterol induced by estradiol, and triglyceride levels are reduced by a similar extent during both the estrogen-only and combined estrogen/Norethisterone treatment phases. Transdermal estradiol appears to have a favourable effect on carbohydrate metabolism and no net adverse effect is observed following coadministration of transdermal Norethisterone. The effects of combined transdermal estradiol/Norethisterone on haemostatic factors and arterial status have yet to be determined. During transdermal estradiol/Norethisterone therapy, vaginal cytology is converted to a pattern similar to that found in premenopausal women, with increased numbers of superficial and decreased numbers of basal and parabasal cells. Transdermal estradiol inhibits bone resorption, as evidenced by a reduction in the urinary ratios of calcium and hydroxyproline to creatinine, and stabilisation of, or small increases in, bone mineral density in postmenopausal women receiving long term treatment. Concomitant progestogen therapy does not appear to impair, and may enhance, the bone conserving effects of estrogens; however, further investigation is necessary to confirm the latter findings. Clinical Use The clinical efficacy of the combined transdermal estradiol/Norethisterone delivery system in preventing endometrial hyperplasia and controlling climacteric symptoms has been investigated in noncomparative clinical trials of up to 3 years’ duration. In most studies, transdermal estradiol 0.05 mg/day was administered for the first 2 weeks of a 28-day cycle, followed by combined transdermal estradiol/Norethisterone 0.05/0.25 mg/day for the last 2 weeks. The combined transdermal estradiol/Norethisterone delivery system provided endometrial protection from unopposed estradiol. Biopsy samples from more than 400 treated women showed proliferative endometrium in 1.5 to 7% and secretory endometrium in 57 to 100%. The incidence of hyperplasia in women receiving this treatment regimen was less than 2%. Sequential transdermal Norethisterone induced a regular vaginal bleeding pattern in about 80% of women. Regular bleeding episodes occurred in 80 to 90% of cycles, with irregular episodes in about 5 to 11%. Amenorrhoea occurred in about 6 to 9% of cycles during therapy. In 2 small studies in which 30 women received continuous transdermal estradiol/Norethisterone, the incidence of amenorrhoea was 53 and 100% after 6 months. Climacteric symptoms including hot flushes, sweating, sleep disturbance, vaginal discomfort, poor concentration and irritability were significantly improved compared with baseline in patients receiving transdermal estradiol with sequential transdermal Norethisterone. Tolerability The most frequently reported adverse effects in women using transdermal estradiol or combined transdermal estradiol/Norethisterone delivery systems are dermatological reactions. Transient mild erythema and itching at the site of application are the most common events. However, severe cutaneous irritation necessitating withdrawal of treatment is experienced by about 6% of patients using the estradiol-only or combined delivery systems. The occurrence of skin reactions can be minimised by selection of new sites when applying patches. Adverse systemic events associated with estrogen or progestogen therapy occurred in a small proportion of women and included breast tenderness, vaginal spotting or bleeding, fluid retention, headache, nausea, gastrointestinal disturbances, bodyweight gain and depression. Of these events, unacceptable vaginal bleeding was the most common reason for patients discontinuing combined estradiol/Norethisterone therapy (affecting 6 to 10%). Transdermal estradiol did not stimulate hepatic metabolism and therefore no increases in plasma levels of renin substrate, sex hormone-, thyroxin-, and cortisol-binding globulins or clotting factors were observed; however, a slight decrease in sex hormone-binding globulins was observed during combined transdermal estradiol/Norethisterone treatment. Dosage and Administration For treatment of postmenopausal symptoms and symptoms of estrogen deficiency due to surgical menopause, and for prevention of postmenopausal osteoporosis in women with an intact uterus, transdermal estradiol 0.05 mg/day is recommended for the first 14 days of a 28-day cycle, followed by 14 days of combined transdermal estradiol 0.05/Norethisterone 0.25 mg/day. The transdermal delivery system should be applied to clean dry intact skin and should be changed twice weekly. Contraindications to the use of estradiol include carcinoma of the breast or endometrium, vaginal bleeding of unknown origin, previous estrogen-associated, or active thromboembolic disease or thrombophlebitis. Caution is advised in patients with past or present endometriosis, uterine leiomyomata, impaired hepatic or renal function, conditions likely to be influenced by fluid retention, or a history of depression or pregnancy-associated jaundice.
Jyoti Kaushal - One of the best experts on this subject based on the ideXlab platform.
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Practice of self-medication of mifepristone-misoprostol drug combination for medical abortion
International Journal of Basic & Clinical Pharmacology, 2014Co-Authors: Sushila Godara, Jyoti KaushalAbstract:Most medical abortion protocols require women to take mifepristone in the hospital setting. The rate of complete abortion up to 63 days’ gestation with mifepristone and misoprostol was reported to be 92-95% using the Food and Drug Administration-approved regimen.1,2 In a recent study, the completion rates of 96-97% was reported in early pregnancy, including pregnancies up to 63 days’ gestation.3 Women choosing medical abortion must consent to undergo vacuum aspiration or dilatation and curettage in cases of incomplete abortion. Medical methods for first trimester abortion have been demonstrated to be both safe and effective. Regimens that combine mifepristone with a prostaglandin analogue such as misoprostol are more efficacious than a prostaglandin alone. Mifepristone, (RU 486, a substitute 19- Norethisterone Derivative)by blocking the progesterone receptors causes estrogen dominance and results in intrauterine fetal death. Simultaneously, it sensitizes the uterus to the activity of the prostaglandin. Thus, a combination of these two drugs is significantly more efficacious for termination of early pregnancy when compared to mifepristone given alone. A regimen that includes mifepristone in a dosage of 200 mg administered orally, followed by misoprostol in a dosage of 800 µg vaginally administered 48 hrs after mifepristone, and is highly effective for medical abortion up to 63 days gestation. This regimen is reported to be the best in most of the studies and moreover mifepristone serum levels do not increase proportionally with increasing oral doses.4 In a study conducted by Schaff et al., it was observed that the success rate was seen in 96-97% of women who were prescribed a combination of mifepristone and misoprostol by authorized personnel at the hospital.3 Women are commonly advised to return for one or more follow-up visits, after 10-14 days because in cases of incomplete abortion she can be managed either expectantly, with an additional dose of misoprostol, or with an aspiration procedure. Women may be given the option of home administration of misoprostol after the initial clinic visit.5 However, the use of mifepristone – misoprostol combination for medical abortion used as self-medication, is rising due to changing socio-cultural practices and increased awareness among women for the termination of early pregnancy up to 63 days. It is observed that many women indulge in the practice of self-medication for termination of pregnancy. They take medicines either from local pharmacists, nurses, on advice of relatives, friends, husband, neighbors, newspaper articles, radio, television, magazines or any other such unauthorized sources for termination of pregnancy which mostly leads to incomplete abortion or many complications. It is observed that only few number of women have complete abortion with self-medication from an unauthorized source and moreover they suffer from pain and heavy bleeding when compared to normal menstrual flow. It is noticed that now-a-days, these drugs are used irrationally and nonjudiciously. Women are thus advised to take proper regimen of mifepristone and misoprostol under the guidance of an authorized practitioner and if they still fail to abort, then they have to undergo surgical evacuation that is, vaccum aspiration for termination of pregnancy.
Sushila Godara - One of the best experts on this subject based on the ideXlab platform.
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Practice of self-medication of mifepristone-misoprostol drug combination for medical abortion
International Journal of Basic & Clinical Pharmacology, 2014Co-Authors: Sushila Godara, Jyoti KaushalAbstract:Most medical abortion protocols require women to take mifepristone in the hospital setting. The rate of complete abortion up to 63 days’ gestation with mifepristone and misoprostol was reported to be 92-95% using the Food and Drug Administration-approved regimen.1,2 In a recent study, the completion rates of 96-97% was reported in early pregnancy, including pregnancies up to 63 days’ gestation.3 Women choosing medical abortion must consent to undergo vacuum aspiration or dilatation and curettage in cases of incomplete abortion. Medical methods for first trimester abortion have been demonstrated to be both safe and effective. Regimens that combine mifepristone with a prostaglandin analogue such as misoprostol are more efficacious than a prostaglandin alone. Mifepristone, (RU 486, a substitute 19- Norethisterone Derivative)by blocking the progesterone receptors causes estrogen dominance and results in intrauterine fetal death. Simultaneously, it sensitizes the uterus to the activity of the prostaglandin. Thus, a combination of these two drugs is significantly more efficacious for termination of early pregnancy when compared to mifepristone given alone. A regimen that includes mifepristone in a dosage of 200 mg administered orally, followed by misoprostol in a dosage of 800 µg vaginally administered 48 hrs after mifepristone, and is highly effective for medical abortion up to 63 days gestation. This regimen is reported to be the best in most of the studies and moreover mifepristone serum levels do not increase proportionally with increasing oral doses.4 In a study conducted by Schaff et al., it was observed that the success rate was seen in 96-97% of women who were prescribed a combination of mifepristone and misoprostol by authorized personnel at the hospital.3 Women are commonly advised to return for one or more follow-up visits, after 10-14 days because in cases of incomplete abortion she can be managed either expectantly, with an additional dose of misoprostol, or with an aspiration procedure. Women may be given the option of home administration of misoprostol after the initial clinic visit.5 However, the use of mifepristone – misoprostol combination for medical abortion used as self-medication, is rising due to changing socio-cultural practices and increased awareness among women for the termination of early pregnancy up to 63 days. It is observed that many women indulge in the practice of self-medication for termination of pregnancy. They take medicines either from local pharmacists, nurses, on advice of relatives, friends, husband, neighbors, newspaper articles, radio, television, magazines or any other such unauthorized sources for termination of pregnancy which mostly leads to incomplete abortion or many complications. It is observed that only few number of women have complete abortion with self-medication from an unauthorized source and moreover they suffer from pain and heavy bleeding when compared to normal menstrual flow. It is noticed that now-a-days, these drugs are used irrationally and nonjudiciously. Women are thus advised to take proper regimen of mifepristone and misoprostol under the guidance of an authorized practitioner and if they still fail to abort, then they have to undergo surgical evacuation that is, vaccum aspiration for termination of pregnancy.
Janice Rymer - One of the best experts on this subject based on the ideXlab platform.
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Why tibolone is different
Reviews in Gynaecological Practice, 2002Co-Authors: Janice RymerAbstract:Abstract Tibolone is a synthetic steroid that is structurally related to the 19 Norethisterone Derivative, such as norethynodrel and Norethisterone. It is taken in a dose of 2.5 mg daily orally and after ingestion is metabolised predominantly to three other steroid molecules. One of these is the δ-4 isomer, which predominates at the endometrium demonstrating progestogenic activity resulting in an atrophic endometrium. Continuous combined hormone replacement therapy is also a non-bleeding therapy, but tibolone is different because it is a synthetic molecule, it has different activities at different tissues, and it has androgenic activities. The commonest reason for prescribing tibolone is for hypo-oestrogenic symptoms, namely vasomotor symptoms and urogenital symptoms. Tibolone demonstrates an oestrogenic effect on both of these symptoms. Tibolone is also prescribed for the protection of the female skeleton and it appears to act as an oestrogen on bone. One of the major concerns of long-term HRT administration is the effect on the breast. In vivo and in vitro pre-clinical studies have suggested that tibolone may demonstrate a protective effect on the breast. There are no human studies to confirm this but looking at mammographic data tibolone does not appear to increase breast density, and clinically does not cause breast tenderness. Tibolone appears to be well tolerated, with break-through bleeding in the first 6 months being the main side-effect. Tibolone is used for women who have no ovarian activity, i.e. women who are at least 1 year since their last menstrual period. However, tibolone can also be used in conjunction with GnRH analogues to relieve hypo-oestrogenic symptoms and protect against bone loss. Tibolone would also be appropriate in women who have had a pelvic clearance for endometriosis as if they were given oestrogen replacement therapy they may experience stimulation of any remaining deposits. Tibolone, therefore, is a synthetic hormone replacement therapy used to relieve hypo-oestrogenic symptoms and protect against bone loss in post-menopausal women.
