Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Norgestimate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1978

Disposition of norgestimate in the presence and absence of ethinyl estradiol after oral administration to humans.

The disposition of radioactivity following oral administration of 14C-norgestimate was compared to that following administration of the drug in combination with 3H-ethinyl estradiol in humans. Seven normal, healthy female subjects were each administered one capsule orally containing 14C-norgestimate either alone (74.4 muCi, 0.50 mg) or in combination (73.5 muCi, 0.49 mg) with 3H-ethinyl estradiol (103 muCi, 0.14 mg) in polyethylene glycol 400. Peak levels of radioactivity due to carbon-14 and tritium in plasma occurred within 2 hr after drug administration, followed by distribution and elimination phases. The mean apparent elimination half-life and mean cumulative elimination of radioactivity in the urine and feces following 14C-norgestimate administration were not significantly different than those following administration of the combination dose. Approximately 50% of the administered radioactivity due to carbon-14 was excreted in the urine following administration of 14C-norgestimate both in the presence and absence of coadministered 3H-ethinyl estradiol.

Administration, Oral↗
PubMed1987

Determination of norgestimate and ethinyl estradiol in tablets by high-performance liquid chromatography.

A rapid, simple, stability-indicating assay procedure for norgestimate [(+)-13-ethyl-17-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one oxime acetate], a new progestational agent, and ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17-diol) in single- and composite-tablet analyses was developed using high-performance liquid chromatography. Norgestimate and ethinyl estradiol were extracted from the tablet matrix with methanol containing an internal standard. An aliquot was chromatographed on a 5-microns, reversed-phase column using water:tetrahydrofuran:methanol solution (65:25:10 v/v/v) as the mobile phase. The selectivity of the chromatographic system for intact norgestimate and ethinyl estradiol was demonstrated by resolving both compounds from various potential degradation products of each compound. An essential property of the chromatographic system was its ability to separate norgestimate as its syn and anti isomers. The method is linear, quantitative, and reproducible.

Drug Stability↗
PubMed2006

Cerebral venous sinus thrombosis in users of four hormonal contraceptives: levonorgestrel-containing oral contraceptives, norgestimate-containing oral contraceptives, desogestrel-containing oral contraceptives and the contraceptive patch.

BACKGROUND: It has been suggested that the risk for cerebral venous sinus thrombosis (CVST) may be greater among users of the contraceptive patch than among users of oral contraceptives (OCs). METHODS: From the PharMetrics database, we identified women aged 15-44 years who filled at least one prescription for either the contraceptive patch or desogestrel-containing, norgestimate-containing or levonorgestrel-containing OCs to assess the risk of CVST. The person-time of current exposure to each study drug, as well as the incidence rates (IRs) and incidence rate ratios (IRRs) of CVST, was calculated. RESULTS: We identified over 1 million users of the four study drugs. There were five cases of CVST among current users of desogestrel, seven cases among current users of norgestimate, two cases among current users of levonorgestrel and none among current users of the contraceptive patch. The IRs per 100,000 woman-years were 2.7 [95% confidence interval (95% CI)=0.9-6.3], 1.6 (95% CI=0.7-3.3), 0.7 (95% CI=0.1-2.4) and 0.0 (95% CI=0.0-4.8), respectively, in users of desogestrel, norgestimate, levonorgestrel and the contraceptive patch. There were two women who had CVST while not currently taking a hormonal contraceptive (IR=0.4 per 100,000 woman-years; 95% CI=0.1-1.3). The IRRs were 4.0 (95% CI=0.7-42.4) for desogestrel-containing versus levonorgestrel-containing OCs, and 2.4 (95% CI=0.5-24.0) for norgestimate-containing versus levonorgestrel-containing OCs. The IRR for the patch could not be calculated. CONCLUSIONS: There is no evidence of an increased risk of CVST in users of the contraceptive patch compared to users of levonorgestrel-containing OCs.

Administration, Cutaneous↗
PubMed2004

The effect of continuous oestradiol with intermittent norgestimate on bone mineral density and bone turnover in post-menopausal women.

OBJECTIVE: To assess in post-menopausal women the efficacy and tolerability of a continuous oestradiol/intermittent norgestimate HRT regimen to prevent and to reverse post-menopausal loss of bone mineral density (BMD) and to determine the effects on serum bone turnover markers markers. METHODS: A 1-year, multicentre, international, placebo-controlled, randomised, double-blind clinical trial was conducted in 146 post-menopausal women with an intact uterus in order to assess the effect on bone loss of continuous oral 17beta-oestradiol (1 mg per day) combined with norgestimate (90 microg per day), for 3 consecutive days out of every 6-day treatment period (E2/iNGM). During a second year extension, all women agreeing to continue were on the E2/iNGM regimen. BMD was assessed prior to treatment and after 1 and 2 years or at the end of treatment in women stopping participation prematurely after at least 6 months of treatment. Serum bone turnover markers were determined prior to and at 1 year of treatment Adverse events were collected at three-monthly intervals during clinic visits over the treatment period. RESULTS: BMD in the lumbar spine, the primary endpoint, was evaluable in 117 subjects completing >6 months of treatment. BMD increased on average by 2.4% in women on the intermittent progestin regimen. It decreased by 1.4% in placebo treated women. The change from baseline and the difference between active and placebo treatment (Delta placebo) were highly significant (P < 0.0001). On E2/iNGM, also the BMD in the total hip increased (+1.49%, Delta placebo 3.73%, P < 0.0001). The serum markers for bone formation osteocalcin and type I collagen N-propeptide were significantly reduced compared to baseline by 31 and 44%, respectively and the bone resorption marker C-terminal crosslinked telopeptide of type I collagen by 59%. Minor increases (<10%) of markers in the placebo group were not significant. During a second year extension of the trial, all subjects were on active treatment. Subjects on placebo who lost (median+/-CI 95%) 0.66% (-2.3 to +0.5) of spine BMD during the first year now gained 4.41% (2.7-7.6). They also gained 1.6% (0.1-0.3.6) in the total hip. Subjects continuously on oestradiol/intermittent norgestimate (E2/iNGM) gained an additional 5.7% (2.3-13.5) in the lumbar spine and +0.1% (-0.6 to +2.2) at the total hip. Side effects reported by women on the intermittent progestin regimen significantly in excess over reports from the placebo group were uterine bleeding, abdominal and breast pain, but not headache. Back pain and weight gain was reported by significantly fewer women on active treatment compared to placebo. CONCLUSION: The continuous oestradiol/intermittent norgestimate HRT regimen is well tolerated, reduces bone turnover and prevents post-menopausal bone loss in healthy post-menopausal women.

Aged↗
PubMedDate not supplied

The duration of response to norgestimate and ethinyl estradiol in the treatment of acne vulgaris.

OBJECTIVE: This was a postmarketing, retrospective, exploratory analysis to investigate the duration of response to a triphasic combination oral contraceptive (OC) (Ortho Tri-Cyclen; Ortho-McNeil Pharmaceutical, Raritan, NJ) [norgestimate-ethinyl estradiol]) in the treatment of moderate acne vulgaris. PROCEDURES: Healthy women with moderate acne vulgaris were enrolled in two 6-month, multicenter, randomized, double-blind, placebo-controlled clinical trials. Subjects received either 3 weeks of active OC treatment (i.e., 0.035 mg ethinyl estradiol plus increasing doses of norgestimate [0.180 mg, 0.215 mg, 0.250 mg]) and 1 week of inactive tablets, or 4 weeks of color-matched placebo tablets. RESULTS: A total of 507 subjects were enrolled in the study. Duration of response was analyzed in subjects with at least slight improvement in global progress of treatment from the earliest cycle showing response (n = 305) and in subjects with at least slight improvement at or before cycle 3 (n = 276); the duration of response was statistically significant in favor of the norgestimate-ethinyl estradiol group in both cases (P < or = .001). The variability of mean percent change in lesions was also statistically significantly greater in the placebo group than in the OC group for total lesions (P < or = .001) and inflammatory lesions (P < or = .001). CONCLUSION: A triphasic combination of norgestimate and ethinyl estradiol lengthens the time interval to recurrence of acne lesions.

Acne Vulgaris↗
PubMed1992

Norgestimate: a clinical overview of a new progestin.

The efficacy and safety of a new monophasic oral contraceptive, norgestimate/ethinyl estradiol, containing the third-generation progestin, norgestimate (250 micrograms), and ethinyl estradiol (35 micrograms), are reviewed. Norgestimate/ethinyl estradiol demonstrates excellent contraceptive efficacy, with a Pearl index of 0.25. Cycle control is reliable, with a low incidence of breakthrough bleeding and spotting. Because of the minimal androgenicity of norgestimate, norgestimate/ethinyl estradiol has a low impact on carbohydrate and lipid metabolism. It neither reduces the vasodilatory and antiaggregatory prostacyclin nor increases its endogenous antagonist, thromboxane. Norgestimate/ethinyl estradiol has no significant effect on blood coagulation factors. All these characteristics suggest that norgestimate/ethinyl estradiol may be associated with a lower risk of cardiovascular disease than other oral contraceptives currently available. Epidemiologic data, however, are not available, and physicians should be reluctant to prescribe it or any oral contraceptive to patients who have a history of vascular or thrombotic disorders.

Female↗
PubMed1995

Lumbar vertebral density and mechanical properties in aged ovariectomized rats treated with estrogen and norethindrone or norgestimate.

OBJECTIVE: This study was designed to investigate the effects of estrogen alone or combined with two different progestins, norethindrone or norgestimate, on bone density and compressive mechanical properties in an aged rat model. STUDY DESIGN: Twenty 11-month-old female Sprague-Dawley rats were sham operated (intact control) and 80 wee ovariectomized. Three groups of 20 ovariectomized rats were implanted with Silastic silicon rubber (Dow Corning, Midland, Mich.) capsules containing 5% estradiol (wt/wt) in cholesterol. All rats in the intact control (group 1) and the ovariectomized (group 2) and the first of the ovariectomized plus estrogen (group 3) groups were injected subcutaneously daily for 6 months with corn oil (vehicle). Two other groups of rats with estrogen capsules received daily injections of norethindrone (3 micrograms/rat/day) or norgestimate (1.5 micrograms/rat/day) in corn oil for 3 days out of every 6 days (interrupted progestin). The effects of these various treatments on bone mineral content and bone mineral density in the vertebrae were measured by dual energy x-ray absorptiometry. The L4 vertebral bodies were also tested to failure in compression. RESULTS: The ovariectomized rats receiving corn oil alone had the lowest bone mineral density compared with intact controls. Estrogen treatment alone resulted in a lower bone mineral density than in the intact controls. In contrast, both interrupted progestin regimens resulted in vertebral bone mass index at the same level as the intact controls. Compression tests revealed that ovariectomized controls also had the lowest modulus of elasticity of all groups. However, unlike bone mineral density, estrogen alone resulted in mechanical properties similar to intact controls, whereas the vertebrae in both interrupted progestin groups had variable mechanical properties compared with the ovariectomized and intact control groups. CONCLUSIONS: We conclude that in this experimental model hormone replacement therapy with estrogen and an androgenic (norethindrone) or nonadrogenic (norgestimate) progestin result in similar bone mineral density and mechanical properties. In addition, both interrupted progestin regimens had a better effect than estrogen alone on vertebral bone density.

Absorptiometry, Photon↗
PubMed1990

Relative binding affinity of norgestimate and other progestins for human sex hormone-binding globulin.

The relative binding affinity of norgestimate for human sex hormone-binding globulin was compared with that of its metabolites and other progestins by measuring their abilities to displace [3H]testosterone from this carrier protein in vitro. Norgestimate and its 17-deacetylated and 3-keto metabolites did not significantly displace [3H]testosterone from sex hormone-binding globulin at concentrations up to 10,000 nM, whereas gestodene, levonorgestrel, and 3-keto desogestrel displaced [3H]testosterone from sex hormone-binding globulin with IC50 concentrations of 23.1, 53.4, and 91.0 nM, respectively. Since it is believed that a progestin may exert androgenic effects by displacing testosterone from sex hormone-binding globulin, thereby increasing circulating levels of free, active testosterone, these data are consistent with the results of preclinical and clinical studies demonstrating the selective progestational activity of norgestimate.

Binding, Competitive↗
PubMed1979

Optimum dosage of an oral contraceptive. A report from the study of seven combinations of norgestimate and ethinyl estradiol.

A statistically designed study was carried out to determine an optimum combination of norgestimate and ethinyl estradiol as an oral contraceptive, based on efficacy, safety, and side-effect patterns. A total of 1,991 patients were studied for more than two years while they were receiving various dosage combinations of these steroids. There were seven dosage combinations studied as part of a statistically orthogonal experimental design, augmented by three combinations near the center. The data arising from these studies were used to fit approximate functions relating the amount of norgestimate and ethinyl estradiol to the rate of spotting and breakthrough bleeding, gastrointestinal disturbance, and pregnancies. These functions, in turn, helped to identify an optimum dosage (0.125 mg. of norgestimate plus 0.035 mg. of ethinyl estradiol) in the entire range of combinations studied.

Adolescent↗
PubMed1997

Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of a triphasic, combination oral contraceptive (OC), (norgestimate-ethinyl estradiol), in comparison with placebo in the treatment of moderate acne vulgaris. METHODS: Two hundred fifty women were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the effectiveness of norgestimate-ethinyl estradiol in the treatment of acne vulgaris. Subjects were 15-49 years old and had moderate acne vulgaris. Each month for 6 months, subjects received either 3 consecutive weeks of active OC treatment followed by 1 week of inactive drug, or 4 consecutive weeks of color-matched placebo tablets. Efficacy was assessed by facial acne lesion counts, the investigator's global assessment, and the subject's self-assessment. Hormone levels were also measured. RESULTS: Despite the large placebo effect inherent in an acne trial (due to, for example, careful skin care, frequent office visits, regression to the mean), of the 164 subjects who completed the study without major protocol deviations, the OC group was significantly better than the placebo group for all primary efficacy measures: inflammatory lesions (mean reduction, 51.4% compared to 34.6%; P = .01), total lesions (mean reduction, 46.4% compared to 33.9%; P = .001); investigator's global assessment (83.3% compared to 62.5%; P = .001). Free testosterone decreased significantly and sex hormone-binding globulin increased significantly in the OC group, but remained unchanged in the placebo group. CONCLUSION: A triphasic combination of norgestimate and ethinyl estradiol is an effective treatment for moderate acne vulgaris in women with no known contraindication to OC therapy.

Acne Vulgaris↗
PubMed2004

Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells.

The function and clinical significance of the androgen receptor (AR) in human breast cancer are still not clear. The synthetic progestins, norgestimate and norelgestromin, were designed to minimize the adverse effects such as acne, hirsuitism and metabolic changes observed with older oral contraceptives while maintaining contraceptive effectiveness and cycle control. AR-mediated effects of these synthetic progestins were studied in an in vitro transactivation assay, employing DNA co-transfection of an AR expression vector and luciferase reporter gene construct in the MDA-MB 231 human breast cancer cell line. Testosterone acetate and 5alpha-dihydrotestosterone induced the reporter gene transcription, whereas incubation of the transfected cells with the natural progestin 17alpha-hydroxyprogesterone did not markedly induce luciferase activity. The progestins norgestimate and norelgestromin exerted a very low androgenic activity. Our data suggest that norgestimate and its metabolite norelgestromin possess weak androgen-like properties. The use of these compounds for clinical application may be of great advantage in the treatment of breast cancer as well as hyperandrogenism in women.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Efficacy and clinical profile of a new oral contraceptive containing norgestimate. U.S. clinical trials.

The search for a highly selective progestin that exerts a potent and targeted progestational response with minimal or absent androgenic effect has paralleled investigation into the possible impact of these agents on cardiovascular disease in women. Such a progestin, norgestimate (NGM), in a dose of 250 micrograms, has been combined with ethinyl estradiol (EE) 35 micrograms in a new oral contraceptive (OC), Ortho-Cyclen or Cilest. Results of two long-term, multicentric clinical trials demonstrate that this formulation is comparable in efficacy to the norgestrel-containing OC Lo/Ovral. There were no statistically significant differences in pregnancy rate, and both OCs were well-tolerated in a large and diverse study population. In several areas, however, the inherently lower androgenicity of the norgestimate OC produced clinical changes compared with the norgestrel formulation. These changes were primarily evident in the more natural menstrual patterns with the norgestimate OC, its less severe impact on the endometrium, and, most important, its positive impact on lipoprotein metabolism. NGM/EE consistently produced statistically significant increases in high density lipoprotein (HDL) and concomitant improvement in the ratio of low density lipoprotein (LDL) to HDL. By cycle 24, this highly predictive parameter of atherosclerotic risk had decreased 7.7% in the NGM/EE group. Conversely, the norgestrel-containing formulation resulted in statistically significant decreases in HDL and increases in the LDL/HDL ratio; by cycle 24, these patients showed an 18.5% increase in the LDL/HDL ratio. All between regimen comparisons of mean changes in the LDL/HDL ratio were statistically significant, from baseline through cycles 3, 6, 12 and 24.

Adolescent↗
PubMed1990

Supportive European data on a new oral contraceptive containing norgestimate.

Several European studies have been conducted to confirm the efficacy, tolerability, and safety of a new oral contraceptive (OC) combining 250 micrograms norgestimate with 35 micrograms ethinyl estradiol (Ortho-Cyclen or Cilest). In a 12-month multicenter German study of 147 women, treatment with this formulation resulted in no pregnancies, a low incidence of side effects, and excellent cycle control. The drug had no effect on estrogen-mediated fibrin formation nor on the activity of coagulation inhibiting or promoting factors. Similarly, the documented low androgenicity of the highly selective progestational agent norgestimate results in a more positive metabolic profile. Glucose, insulin, and hemoglobin A1c concentrations measured before and after glucose loading were not adversely affected by treatment with the norgestimate-containing OC, and all changes were reversible on its discontinuation. In addition, lipid metabolism was positively influenced by the drug. Low-density lipoprotein cholesterol, a known risk factor for cardiovascular disease, was reduced while the cardioprotective lipid fraction, high-density lipoprotein cholesterol, was increased. Clinical trials to determine the OC's effects on coagulation, endocrine function, and carbohydrate and lipid metabolism are reviewed. Also discussed are several studies demonstrating the formulation's unique endometrial effects, which may possibly be related to its low androgenic activity and consequent low incidence of breakthrough bleeding and amenorrhea.

Adolescent↗
PubMed2000

[Prediction of the effect of a triphasic contraceptive agent with norgestimate on acne].

OBJECTIVE: Prediction of complexion changes in users of triphasic oral contraceptive containing norgestimate. DESIGN: Analysis of data from a prospective multicentre open study. SETTING: Department of Obstetrics and Gynaecology, Charles University, Prague. METHODS: Acne severity was evaluated in users of a triphasic norgestimate-containing contraceptive within a six month period. Based on subjective evaluation of acne, three subgroups of patients were selected: A) users where acne improved or disappeared; B) users in whom acne deteriorated, C) users who newly developed acne. Differences between group A and the other groups were established in the proportion or distribution of parameters related to the etiology of acne: age, weight, weight changes during the study, presence of hirsutism, presence of a regular menstrual cycle prior to the start of hormonal contraception use, and smoking. RESULTS: The effect of the pill use on acne was assessed in a total of 3,990 women. Out of 1,201 women with acne before the start of the study, improvement or disappearance of acne during the study was reported by 940 users (subgroup A) (78.27%). In 221 women (18.40%), the extent of acne remained unaltered whereas it increased (subgroup B) in only 30 women (2.50%). Acne newly developed during the study in 49 women (subgroup C), i.e., in 1.2% of the whole group. Users showing deterioration of acne (subgroup B) were found to have hirsutism less frequently. The subgroup even showed a decrease in mean weight during the study. Users with newly developed acne were--compared with subgroup A--significantly older, had a lower weight at the start of the study, and showed a higher frequency of regular menstrual cycles prior to starting hormonal contraception. The differences in the incidence of clinical parameters in the subgroups reached only borderline statistical significance and, hence, are not relevant. CONCLUSION: An extensive multicentric study confirmed the beneficial effect of a triphasic norgestimate-containing contraceptive on complexion. The presence of clinical parameters related to the etiology of acne does not allow to predict the individual response of the skin to hormonal therapy.

Acne Vulgaris↗
PubMed1994

Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate.

Both monophasic and triphasic formulations of ethinyl estradiol plus norgestimate, a progestin with marked progesterone-receptor affinity and minimal androgen-receptor affinity, have been evaluated in numerous clinical studies designed to determine if norgestimate's receptor-binding profile provides enhanced safety without a reduction in efficacy. To date clinical trials have shown that both formulations of ethinyl estradiol/norgestimate offer contraceptive efficacy equivalent to that of other oral contraceptives. Monophasic ethinyl estradiol/norgestimate was associated with an incidence of breakthrough bleeding and spotting similar to that of monophasic ethinyl estradiol/norgestrel and an incidence of amenorrhea less than that of ethinyl estradiol/norgestrel. Cycle control with triphasic ethinyl estradiol/norgestimate was similar to that with monophasic ethinyl estradiol/norgestimate. Weight gain and elevated blood pressure were insignificant in clinical trials with both fixed-dose and phasic ethinyl estradiol/norgestimate formulations. Perhaps of greatest importance, both monophasic and triphasic ethinyl estradiol/norgestimate formulations consistently showed favorable impact on metabolic parameters, including elevations in serum high-density lipoprotein cholesterol, and reductions in the low-density lipoprotein/high-density lipoprotein ratio, the parameter considered most sensitive for atherosclerotic risk. Both monophasic and triphasic ethinyl estradiol/norgestimate formulations were associated with minimal and clinically neutral effects on carbohydrate metabolism.

Contraceptives, Oral, Combined↗
PubMed1997

Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris.

BACKGROUND: An excess of androgen is believed to contribute to development of acne in some patients. Because oral contraceptives (OCs) may reduce the active androgen level, hormonal therapy with OCs has been used successfully to treat patients with acne, although this treatment has previously not been studied in placebo-controlled trials. OBJECTIVE: Our purpose was to evaluate the efficacy of a triphasic, combination OC (ORTHO TRI-CYCLEN [Ortho-McNeil Pharmaceutical, Raritan, N.J.], norgestimate/ethinyl estradiol) compared with placebo in the treatment of moderate acne vulgaris. METHODS: Two hundred fifty-seven healthy female subjects, 15 to 49 years of age with moderate acne vulgaris, were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial. Each month for 6 months, subjects received either 3 consecutive weeks of the OC (i.e., tablets containing a fixed dose of ethinyl estradiol [0.035 mg] and increasing doses of norgestimate [0.180 mg, 0.215 mg, 0.250 mg]) followed by 7 days of inactive drug or placebo (color-matched tablets). Efficacy was assessed by facial acne lesion counts, an investigator's global assessment, a subject's self-assessment, and an analysis of within-cycle variation (cycle 6) in lesion counts. RESULTS: Of the 160 subjects in whom efficacy could be evaluated, the OC group showed a statistically significantly greater improvement than the placebo group for all primary efficacy measures. The mean decrease in inflammatory lesion count from baseline to cycle 6 was 11.8 (62.0%) versus 7.6 (38.6%) (p = 0.0001), and the mean decrease in total lesion count was 29.1 (53.1%) versus 14.1 (26.8%) (p = 0.0001) in the OC and placebo groups, respectively. In the investigator's global assessment, 93.7% of the active treatment group versus 65.4% of the placebo group were rated as improved at the end of the study (p < 0.001). Six of the seven secondary efficacy measures (total comedones, open comedones, closed comedones, papules, pustules, and the subject's self-assessment of study treatment) were also significantly more favorable in the OC group compared with the placebo group. CONCLUSION: An OC containing 0.035 mg of ethinyl estradiol combined with the triphasic regimen of norgestimate is a safe and effective treatment of moderate acne vulgaris in women with no known contraindication to OC therapy.

Acne Vulgaris↗
PubMed1992

The new era in oral contraception: pills containing gestodene, norgestimate, and desogestrel.

The latest advance in the 30-year evolution of oral contraceptives (OCs) is the development of three new progestogens: desogestrel, norgestimate, and gestodene. These three new agents are derivatives of levonorgestrel, a gonane hormone, and have been used to develop pills that provide effective pregnancy prevention at lower doses than oral contraceptives using the older steroids. Desogestrel is a prohormone that must first be metabolized into its biologically active form. Norgestimate is already active, but it will be metabolized in part to levonorgestrel. Gestodene is biologically active in its native form. Among the improvements in metabolic parameters seen with this new generation of progestogens are a lack of impact on blood pressure, a balanced effect on coagulation, and a reduced impact on carbohydrate metabolism compared with earlier, higher-dose formulations. The new pills also seem to produce no negative effects on lipid and lipoprotein biosynthesis, and perhaps even improve the ratio of low-density lipoprotein to high-density lipoprotein. Cycle control with all three progestogens is improved, with much lower incidence of intermenstrual bleeding (IMB). Efficacy is as good as with other OCs. Another benefit of the new low-dose progestogens, however, is the low incidence of minor side effects observed in women using these contraceptives. Low incidences of weight gain, headache, and nausea were reported, and the dropout rate because of side effects was low in both international and US trials. Serious side effects are rarely seen with pills containing the new progestogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraceptives, Oral, Combined↗
PubMed1984

Biotransformation of norgestimate in women.

The metabolism of norgestimate (ORF-10131; 14C-d-13-ethyl-17-acetoxy-18,19-dinor-17 alpha-pregn-4-en-20- yn -3-oxime) was studied in humans. Compound labeled with carbon-14 in the 17 alpha-ethynyl group was administered to four female subjects. An average of 46.8 percent of the administered radioactivity was excreted in the urine and 36.8 percent in the feces over a two-week collection period. About 12 percent of the urinary radioactivity represented freely extractable metabolites and another 57 percent consisted of extractable material released by enzyme hydrolysis. The ethynylated metabolites of norgestimate were separated from endogenous compounds and non- ethynylated metabolites by silver- sulfoethyl cellulose column chromatography. Metabolites were subsequently isolated by high performance liquid chromatography and thin layer chromatography. The identification of five urinary metabolites was accomplished by combined gas-liquid chromatography/mass spectrometry. These metabolites include norgestrel, 16 beta- hydroxynorgestrel , 2 alpha- hydroxynorgestrel , 3 alpha, 5 beta- tetrahydronorgestrel , and a fifth trihydroxylated metabolite of undetermined stereochemical configuration; 3,16-dihydroxy-5- tetrahydronorgestrel .

Biotransformation↗