Norgestrel Research Articles

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy(HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increasedin the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatmentgroups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previousHRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significantreduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison withthe EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol.The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.

A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind ,randomized ,multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2) and 0.5 mg trimegestone (TMG) with a standard hormone replacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment of climacteric symptoms. The study was conducted over 13 cycles ,each of 28 days ,and involved 634 subjects, of whom 481 completed the study. The primary efficacy variable was the percentage of subjects who showed at least a 50% reduction from baseline in the mean daily number of hot flushes in cycle 3. This was observed in 98.5% of the subjects in the E2 + TMG group and 93.3% of the subjects in the E2V + NG group (95% confidence interval of the difference ,8.6 ,1.9). Significant differences in favor of the E2 + TMG combination were observed in the reduction in the mean daily number and severity of hot flushes ,and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment. There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerated and the incidences of adverse events were similar in the two treatment groups. Breast pain was the main adverse event ,possibly related to treatment that resulted in discontinuation. The mean number of bleeding days per cycle was significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and comparable in both treatment groups. It was concluded that the E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms ,and that its bleeding profile was favorable.

A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind ,randomized ,multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2) and 0.5 mg trimegestone (TMG) with a standard hormonereplacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment of climacteric symptoms. The study was conducted over 13 cycles ,each of 28 days ,and involved 634 subjects,of whom 481 completed the study. The primary efficacy variable was the percentage of subjects who showed at least a 50% reduction from baseline in the mean daily number of hot flushes in cycle 3. This wasobserved in 98.5% of the subjects in the E2 + TMG group and 93.3% of the subjects in the E2V + NG group (95% confidence interval of the difference ,8.6 ,1.9). Significant differences in favor of the E2+ TMG combination were observed in the reduction in the mean daily number and severity of hot flushes ,and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment.There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerated and the incidences ofadverse events were similar in the two treatment groups. Breast pain was the main adverse event ,possibly related to treatment that resulted in discontinuation. The mean number of bleeding days per cyclewas significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and comparable in both treatment groups. It was concluded thatthe E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms ,and that its bleeding profile was favorable.

Emergency Contraception: Still Effective After 72 Hours?

The effectiveness of emergency contraception (EC) -- including norgestrel plus ethinyl estradiol (the Yuzpe method) and levonorgestrel alone -- within 72 hours after unprotected coitus has been documented by well-designed clinical trials. These Canadian authors conducted an observational study to determine whether EC would be effective for preventing pregnancy if taken longer than 72 hours after unprotected intercourse. The researchers compared 131 …

Determination of norgestimate and its metabolites in human serum using high-performance liquid chromatography with tandem mass spectrometric detection

A rapid and reliable analytical method is described for the simultaneous determination of a synthetic progestin norgestimate (NGM), and its metabolites, 17-deacetylnorgestimate (17-DA-NGM), 3-ketonorgestimate (3-keto-NGM) and norgestrel (NGL) in human serum using reversed phase high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS-MS) detection. The assay was linear over the concentration ranges of 0.1–5.0 ng/ml for 17-DA-NGM and NGL and 0.5–5.0 ng/ml for NGM and 3-keto-NGM. The inter-assay reproducibility was consistently less than 10%. The overall recovery of the analytes ranged from 72 to 92%. Serum profiles following oral administration of norgestimate to female volunteers are presented.

Emergency Contraception: Two Regimens

Emergency contraception is becoming more widely available. The Yuzpe regimen (combined OCs -- ethinylestradiol and levonorgestrel or dl-norgestrel) is

Endocrine effects in Asian postmenopausal women treated with 5H D 461 M and Prempak-C

We reported the results of a randomized cross-over study comparing SH D 461 M (Climen) and Prempak-C in 38 postmenopausal women who were established users of hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate. Prempak-C, on the other hand, is a regime consisting of 28 tablets of 0.625 mg conjugated equine estrogens (CEE); the last 12 tablets are taken together with 0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen for 6 months and then crossed-over to Prempak-C, for the next 6 months; patients in Sequence II, followed the reverse order. Following Climen treatment, significantly higher levels ( P < 0.05, t-test) of sex hormone binding globulin (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No significant differences in follicle stimulating hormone (FSH), corticosteroid binding globulin (CBG), renin, angiotensinogen, angiotensin-I and aldosterone levels between the two treatment regimes were noted. While both regimes were effective in reducing menopausal symptoms, none of the regimes could eliminate all symptoms completely. Treatment with Climen appeared to result in less frequent occurrences of some symptoms. During periods of no estrogen (only true for Climen) as well as periods of maximum progestagen and estrogen (P and E), subjects on Climen had significantly lower incidence of some of the symptoms (backache, lack of concentration, lethargy and swelling) when compared to those on Prempak-C. The observed lower incidence of some symptoms during periods of no estrogen in the Climen as compared to the Prempak-C regimes would dispel the notion that an estrogen tablet-free interval would result in more frequent occurrences of some menopausal symptoms. This observation could be due, in part, to the higher estrogenicity of Climen, as indicated by higher SHBG levels following its treatment. Whether cyproterone acetate, which is non-androgenic and, in addition, anti-androgenic as compared to norgestrel, has a part in better symptom relief remains speculative.

The Next Generation of Oral Contraceptives in Clinical Practice: Chairman's Summary

Oral contraceptives with low-dose formulations have mitigated cardiovascular (CV) disease risk. High-density lipoprotein (HDL) had cardioprotective properties whereas low-density lipoprotein (LDL) is positively correlated with high risk. Half of the women have a lipid problem by the age of 30. The benefits of early lipid modification will accrue later in life because of reduced CV morbidity and mortality. The evolution of OCs improved the benefit-to-risk ratio. The risk of venous thromboembolic events has dropped by lowering the dose of estrogen to 30 or 35 mcg. Beta 1 and 2 agonists to H2 receptor blockers are a promising solution to the problem of OC-related CV risk. Norgestimate a selective new progestin has strong progestational potency and antiovulatory activity. 250 mcg norgestimate (NGM) was combined with 35 mcg ethinyl estradiol (EE) in a new formulation NGM/EE and compared to a norgestrel (NG) containing compound Lo/Ovral (NG/EE). The effect of NGM/EE on ovulation suppression was equivalent to NG/EE. The LDL/HDL ratio changed as a result of the increase of HDL in NGM/EE patients and the rise of LDL in NG/EE patients. NGM/EE positively affected lipid parameters increasing HDL levels with a concomitant improvement of the LDL/HDL ratio. Obstetricians and gynecologists have the duty of assessing cardiovascular risk for the sake of the long-term health of women. Effects of lipid-lowering OCs on cardiovascular morbidity and morality are still a long way off from exact quantification. Thus the progestational selectivity of norgestimate will be a valuable alternative by obviating problems associated with oral contraception.

Effect of progestins, estradiol, and coenzymes nad and nadph on the interconversion of estradiol and estrone in rabbit uterus in vitro

The biotransformation of estradiol (E2) and estrone (E1) in the uterus of rabbits treated with norgestrel (NG), norethindrone (NET), norethindrone acetate(NETA), progesterone (P4), and E2 either by subcutaneous injection in oil or by intrauterine steroid-releasing silastic implants was carried out under an in vitro shortterm incubation system. The studies have shown that E2 stimulates 17 β-hydroxysteroid dehydrogenase (17β-OHSD) much more than P4 as compared to untreated controls. The kinetic studies on E2 metabolism in the presence of added coenzyme NAD showed an initial rapid estrone formation and a gradual reconversion of E1 to E2. The addition of NADPH, ATP, and glucose-6-phosphate facilitates the reconversion of E1 to E2. The interconversion of E2 and estrone in the presence of coenzymes was five- to ten-fold higher in the endometrium than in the myometrium per milligram protein. Both E2 and progestins stimulate the uterine 17β-OHSD activity in rabbit uterus. This study further suggested that the hormoneinduced metabolism of estradiol and estrone in the rabbit uterus is essentially modulated by the availability of coenzymes.

Suppression of reproductive function in autoimmune NZB/W mice: effective doses of four contraceptive steroids.

Oral contraceptives have been implicated in causing flares of systemic lupus erythematosus in humans, and studies of these agents in the NZB/W mouse model of lupus may help to elucidate mechanisms responsible for disease activation. To define doses which effectively suppress reproductive function in NZB/W mice, we implanted groups of NZB/W females with Silastic capsules containing increasing doses of four compounds: norethindrone (NE) 0.5-5.0 mg, norgestrel (NG) 1.0-7.5 mg, medroxyprogesterone (MP) 0.5-20.0 mg, and ethinyl estradiol (EE) 0.5-5.0 mg. Controls received empty implants. Serum concentrations of LH and FSH, uterine weight, endometrial proliferation, and luteal tissue were assessed after 3 weeks of treatment. Based upon these parameters, we determined that effective doses were 5.0 mg NE, 7.5 mg NG, and 0.5 mg EE given as single implants and 10.0 mg MP given in two 5.0-mg implants. This is the first dosing study of contraceptive steroids in a murine model of lupus. Effective, nontoxic doses of these drugs can now be employed in studies of interactions between gonadal hormones and autoimmunity.

Failure with the new triphasic oral contraceptive Logynon

Failure with the new triphasic oral contraceptive Logynon

Uterine and kidney aspartate aminotransferase activity in ethinylestradiol- and norgestrel-treated rats

Aspartate aminotransferase (AST) activity was measured in the kidneys and uteri of mature female rats to determine what effect, if any, treatment with ethinylestradiol(EE), norgestrel (NOR) or a combination of both hormones might have on the relationship of pyridoxal-PO 4 to AST activity. Treatment with EE had no effect on the degree of saturation of kidney AST with pyridoxal-PO 4, AST activity/mg kidney or total kidney AST activity compared to controls. Kidney weight was, however, significantly elevated (P < 0.05). The same AST parameters were elevated (P < 0.05) in rats treated with NOR or EE + NOR. Saturation of AST by pyridoxal-PO 4 was not altered by hormone treatment in uteri, but AST activity/mg uterus and total uterine activity were lowered by NOR or EE + NOR treatment. Exposure to EE alone elevated these last two parameters. It is noteworthy that the same hormone can both stimulate or inhibit AST, depending on the organ in question. Since progestindominant contraceptives are becoming more commonplace, it is important to observe that the progestin was more effective in altering AST parameters than was the estrogen.