SEARCH · PubMed Health

Results for “Norethindrone Acetate”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources

PubMed1987

Effects of progestogens on lipemia and lipolysis in rat: effects of progesterone, megestrol acetate, norethindrone acetate, and nomegestrol acetate.

Effects of 4 progestogens at equal dosages (5 mg/kg/day) on lipid metabolism and plasma glucose levels of adult female rats were compared. The 4 progestogens studied were progesterone (P) by SC injection, and megestrol acetate (MEG), norethindrone acetate (NOR), and nomegestrol acetate (NOM) PO. MEG, a 17 alpha-hydroxyprogesterone derivative, induced significant increases in glucose, total and high-density lipid (HDL) cholesterol, triglyceride, and phospholipid plasma levels. Treatment with NOR, a 19-nortestosterone derivative, resulted in a reduced gain in body wt and in a marked decrease in all plasma lipid parameters. The 19-norprogesterone derivative NOM, like P, did not alter lipid or glucose metabolism, despite a significant increase in body wt gain. In particular, no reduction in the HDL cholesterol level occurred. Plasma and tissue lipolytic activities remained unchanged. The results of this study confirm interest in the therapeutic class of 19-norprogesterone-derived progestogens, exemplified by NOM, with respect to their lack of metabolic side effects.

Animals↗

PubMed1992

Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis.

OBJECTIVES: This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. STUDY DESIGN: Seventy-nine postmenopausal women on sequential estrogen-progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. RESULTS: Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. CONCLUSIONS: Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised.

Amenorrhea↗

PubMed1982

Pharmacokinetics of norethindrone acetate in women after the insertion of a single subdermal implant releasing norethindrone acetate.

The metabolic clearance rate (MCR) of norethindrone acetate (NETA) and norethindrone (NET) levels in plasma were studied after an iv injection of [3H]NETA in three women before and at 1 week, 1, 2 and 6 months following the insertion of a single silastic subdermal implant releasing microquantities of NETA. No significant change in the MCR of NETA was observed at 1 week (459 +/- 72 1/day), 1 month (489 +/- 113 1/day) and 2 months (522 +/- 144 1/day) compared with that of control (525 +/- 108 1/day). However, MCR of NETA showed significant increase in women exposed to continuous presence of NETA for a period of 6 months (608 +/- 121 1/day; P less than 0.025). NETA was rapidly and extensively metabolized into NET. At 1 week, 1, 2 and 6 months of study, NET was observed to be present in higher amounts compared with NETA. The production rate (PR) of progesterone decreased significantly at 2 and 6 months of NETA implant insertion compared with the PR before the insertion of implant.

Adult↗

PubMed1983

Norethindrone in serum after use of an oral contraceptive containing norethindrone acetate.

The availability of norethindrone (NET) in serum was studied in 8 women after daily administration of a combination oral contraceptive pill (MinovlarR) containing 1 mg norethindrone acetate (NETA) and 50 micrograms ethinyl estradiol (EE2) from day 5 to day 25 of the menstrual cycle. The pill was taken daily at 9:30 a.m. after a light breakfast and blood samples were collected at 3 hr on alternate days and at 24 hr on other days after ingestion of the pill. On day 12 or day 15 of the first treatment cycle, serial blood samples were also collected at 1/2, 1, 2, 4, 6, 8 and 24 hr after taking the pill. Serum NET levels were estimated by the radioimmunoassay (RIA) technique. The plot of serum NET concentration versus time (0-24 hr) profile showed a rapid absorption of steroid and a peak NET concentration (18.3 +/- 4.8 ng/ml) reached at 2 hr after ingestion of the pill. By linear regression analysis of data (y = 0.27 + 0.12x; r = 0.95), it was observed that the serum NET level was initially about 1 ng/ml. Thereafter, it increased by 0.12 ng/ml per day up to 3.5 ng/ml by the end of 21 days' treatment with oral pills. The serum NET concentration decay slope fitted a two-compartment open model with an initial rapid decay (half-life of 1.2 +/- 0.1 hr) followed by a slower beta-phase with a half-life of 8.5 +/- 1.5 hr. The study revealed that there was an accumulation of norethindrone in plasma during the treatment period and this suggests the possibility of exploring a reduction in the dose of this preparation so as to achieve the optimum NET concentration for contraception, and thereby avoiding unwanted steroid accumulation in the plasma of women.

Adult↗

PubMed1983

Norethindrone acetate inhibition of triglyceride synthesis and release by rat hepatocytes.

The progestin, norethindrone acetate has been widely administered to patients in the form of oral contraceptives; however, its hypolipemic action has received little study. This report describes the effects of conventional doses of norethindrone acetate (100 micrograms/day.kg body weight 0.75) on rat plasma lipid levels in vivo as well as the mechanism of action on triglyceride metabolism in isolated hepatocytes in vitro. Norethindrone acetate administration led to significant and proportional reductions of the concentrations of triglycerides, cholesterol and phospholipids of plasma lipoproteins of density less than 1.006 of rats fed a high carbohydrate diet. Norethindrone acetate (0.1 mM) also significantly inhibited the incorporation of both [9,10(-3)H] palmitate and [U-14C]glycerol into triglycerides of isolated hepatocytes from fed rats, by 11 to 16% (P less than 0.001). Release of labeled triglycerides from the isolated hepatocytes was similarly inhibited, 21% and 46%, respectively (P less than 0.05). At the higher concentration of 1.0 mM, norethindrone acetate inhibited the incorporation of [2(-3)H]glycerol into hepatocytic triglycerides by 35-39% (P less than 0.05). The present findings suggest that inhibition of hepatic triglyceride synthesis can account for the reduction of hepatic triglyceride secretion and for at least part of the lowering of plasma VLDL levels which occurs during administration of norethindrone acetate in the rat.

Animals↗

PubMed1996

A combination of norethindrone acetate and leuprolide acetate blocks the gonadotrophin-releasing hormone agonistic response and minimizes cyst formation during ovarian stimulation.

A protocol utilizing both leuprolide acetate (LA) and norethindrone acetate (NETA) in subjects undergoing ovarian suppression prior to follicle aspiration proved more effective than LA alone in reducing the incidence of ovarian cyst formation without affecting clinical outcome. Patients (n = 105) undergoing ovarian stimulation followed by follicle aspiration and in-vitro fertilization (IVF) were prospectively randomized and studied. Study measures included ovarian suppression days, days of human menopausal gonadotrophin (HMG) stimulation, serum oestradiol concentrations, number of cycles developing de novo cysts (>15 mm), number of induced flare responses (day 8 oestradiol >=50 pg/ml), number of office visits, total dose exogenous gonadotrophins, number oocytes retrieved, and clinical pregnancy and delivery rates per retrieval. Patients undergoing IVF received either LA alone (n = 58; controls) or LA and NETA (n = 47; study group) for the first 8 days of their cycle. Results comparing NETA/LA versus LA demonstrated: serum oestradiol 20.7 +/- 3.9 versus 57.3 +/- 9.4 pg/ml respectively on day 8 of ovarian suppression (P P < 0.01); and only three individuals (6.4%) using NETA/LA developed ovarian cysts >15 mm compared to 15 (25.9%) controls (P < 0.01). No differences were observed for days of stimulation, peak oestradiol attained, total dosage of exogenous gonadotrophins, or number of aspirated oocytes. Neither were there differences in the clinical pregnancy (26.8 versus 22.6%) nor in delivery rates (19.5 versus 20. 8%). We conclude that the addition of NETA to LA enhances ovarian suppression and lessens ovarian cyst formation, thereby significantly decreasing the overall cost per cycle.

Adult↗

PubMed1979

Pharmacokinetics of norethindrone acetate in women.

The plasma half-life, MCR and plasma metabolite levels at various time intervals have been studied in six women after an intravenous injection of 3H-norethindrone acetate. The disappearance curve due to norethindrone acetate showed an initial rapid disappearance of 3H with an average half-life of 7.5 minutes and a subsequent slow disapperance with a half-life of 51.5 hours. Norethindrone acetate was cleared from the plasma with an average MCR of 495 L/day. Norethindrone acetate is rapidly metabolised after an intravenous injection. Norethindrone, the main metabolite, disappears from the plasma with an average half-life of 34.8 hours. Norethindrone maintains a high level compared with norethindrone acetate at all time intervals up to 24 hours and an equilibrium is reached between the two at 24 to 48 hours.

Acetates↗

PubMed1978

Radioimmunoassay of norethindrone : serum levels of norethindrone in lactating women after insertion of a single Silastic implant releasing norethindrone acetate.

A specific radioimmunoassay was developed for the estimation of norethindrone levels in the serum of lactating women. A conjugate of norethindrone-3-BSA was synthesized and antiserum raised against it in rabbits. The antiserum showed high affinity (1.5 x 10(9)M/L) and titer and was specific. The sensitivity of the assay was 125 pg/ml serum. Serum levels of norethindrone were estimated in 25 lactating women, inserted with subdermal implant releasing about 150 ug of norethindrone acetate daily. The norethindrone levels were initially high in the first two months. From there onwards the levels of norethindrone remained constant with an average value of 1.0 ng/ml up to six months. These values were comparable to those obtained in non-lactating women. Thus, lactation does not seem to alter or affect the release of norethindrone acetate from the subdermal implant or its metabolism.

Animals↗

PubMed1979

Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed siwne.

The effects of conventional doses of two synthetic contraceptive steroids on the concentration and rate of secretion of plasma triglycerides from the splanchnic region were investigated. Studies were undertaken in miniature swine under steady state conditions produced by prolonged constant hypercaloric intravenous infusions of glucose. The steroids, alone or in combination, were administered with the high carbohydrate diet for at least 2 weeks prior to study of splanchnic metabolism and were also infused intravenously during the studies. Splanchnic triglyceride secretion was determined from measurements of plasma flow and transsplanchnic radiochemical gradients of plasma triglycerides. Compared with studies in the untreated animal, norethindrone acetate significantly reduced the arterial concentration (1.1 +/- 0.1 vs. 0.7 +/- 0.1 mM) and rate of splanchnic secretion of plasma triglyceride fatty acids (2.0 +/- 0.4 vs. 0.8 +/- 0.1 micro mol/min.kg body wt(0.75)) and decreased the percent of free fatty acids entering the splanchnic region that was converted to plasma triglycerides (22 +/- 5 vs. 13 +/- 3%, P < 0.05). Ethynylestradiol, in the dose employed, had no significant effect on these variables; however, ethynylestradiol and norethindrone acetate together gave responses similar to norethindrone acetate alone. When the glucose was given intraduodenally vs. intravenously, values for splanchnic metabolism of triglycerides were unchanged. The hypolipemic effect of norethindrone acetate in glucose-fed swine was attributable to inhibition of hepatic triglyceride secretion.-Wolfe, B. M., and D. M. Grace. Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed swine.

Animals↗

PubMed1991

Androgen synthesis in human fetal testis exposed in utero to a combination of norethindrone acetate and ethinyl estradiol.

The effect of norethindrone acetate (NET-Ac) and ethinyl estradiol (EE2) on the 3 beta-hydroxysteroid dehydrogenase (HSD)-delta5-isomerase complex of the human fetal testis was studied by administration of 20 mg NET-Ac and 0.04 mg EE2 p.o on a single day to 4 women, pregnant 10-16 weeks, before abortion was induced, the other 4 patients serving as controls. Testosterone and androstenedione formation from radioactive dehydroepiandrosterone was measured in 8 fetuses by incubation of testicular tissue in vitro. The presence of normal feta Leydig cells was confirmed by electron microscopy. There was no difference between the enzyme activities of testicles in the experimental and control groups. The findins give values of 3 beta-HSD-isomerase activity in human fetal testis and suggest that the steroidogenic function of the fetal testis exposed for a short time to normally used contraceptive steroids remains at the same magnitude.

Androgens↗

PubMed1993

Norethindrone acetate only partially protects the skeleton of rats treated with the LHRH agonist buserelin from oestrogen-deficiency osteopaenia.

In women with endometriosis there is concern that therapeutic use of LH-releasing hormone (LHRH) analogues, to lower ovarian oestrogen production and control endometrial hyperplasia, leads to unwanted oestrogen-deficiency bone loss. We have developed an animal model of this LHRH-mediated oestrogen-deficiency bone loss in the rat, using buserelin. The aim was to use this model to determine whether the progestogen, norethindrone acetate, could counter oestrogen-deficiency bone loss associated with prolonged treatment with the LHRH agonist buserelin. Four groups of animals which had their bones labelled with 45Ca were studied for 4 weeks: group A, control; group B, buserelin treated; group C, norethindrone acetate treated; group D, norethindrone acetate+buserelin treated. Buserelin was given daily (19.2 pmol/kg body wt); norethindrone was given orally three times/week (1.47 mumol/kg body wt). Bone resorption was monitored by measuring the urinary excretion of hydroxyproline and 45Ca and bone 45Ca content. Buserelin-treated rats developed similarly depressed plasma oestradiol-17 beta values in the presence and absence of progestogen, and both groups given buserelin had significantly smaller uteri than controls or rats given norethindrone without buserelin. However, norethindrone did not prevent buserelin-mediated increases in bone resorption. At the end of the study total body calcium values (mean +/- S.D.) in the four groups were (mg) respectively; 2594 +/- 123; 2260 +/- 92 (P < 0.001 compared with controls); 2616 +/- 221; 2415 +/- 130 (P < 0.02 compared with controls). Rats given norethindrone and buserelin in combination had higher values (P < 0.02) than animals given buserelin alone, but significantly less total body calcium than controls (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1979

Metabolic and endocrine studies in women using norethindrone acetate implant.

Subcutaneously administered implant-D containing 40 mg of Norethindrone acetate in a single silastic implant was offered to 79 subjects who desired spacing of their family. The effect of constant release of steroid from this device on metabolic and endocrine functions was studied. Each subject in the pretreatment state served as her own control. The device was removed at 8 months initially and subsequently at 5-6 months. The clinical acceptability of this method was fairly high. The results reported in this study show that Norethindrone acetate administered in this way did not cause any adverse reactions on endocrine and metabolic functions as gauged by the parameters analysed.

Adult↗

PubMed1991

Bioavailability of norethindrone and menstrual pattern after insertion of norethindrone acetate implants in rhesus monkeys.

Subdermal silastic implants releasing norethindrone acetate were inserted in five rhesus monkeys for a period of seven months. The serum norethindrone (NET) levels were estimated from blood samples collected fortnightly. There was an initial high level of NET followed by fluctuating levels of NET in 4 out of five monkeys. The serum NET values showed individual variation between time periods as well as between monkeys. The analysis of menstrual cycles showed initial amenorrhoea up to day 120-140 in four out of five monkeys. Only one monkey showed vaginal bleeding pattern comparable to normal menstrual cycles; this monkey had serum NET levels less than 10 ng/ml. The pharmacokinetic and pharmacodynamic parameters were similar to those reported in the human female.

Amenorrhea↗

PubMed1990

The optimal dose of oral norethindrone acetate for addition to transdermal estradiol: a multicenter study.

The effects of adding one of three doses (0.5, 0.75, or 1.0 mg/d) of norethindrone acetate for 12 days each month to continuous, transdermal estradiol (0.05 mg/d) have been determined in a prospective, randomized, multicenter study. Significant symptomatic and psychological improvements were observed and, with one exception, were not opposed by the added progestogen. Distinct redness at the site of last patch application was reported by 10% of patients and faint erythema by 30%. However, less than 5% of patients discontinued treatment because of skin problems. Breakthrough bleeding occurred infrequently and all three doses of norethindrone acetate induced a regular pattern of bleeding with secretory transformation in the endometrium. There was no hyperplasia or carcinoma.

Administration, Cutaneous↗

PubMed1989

Programming of ovarian stimulation with norethindrone acetate in IVF/GIFT cycles.

Twenty patients were given norethindrone acetate (NET) to program the initiation of controlled ovarian hyperstimulation and to coordinate follicular aspiration with surgery to obtain spermatozoa from the husband. Patients received NET, 10 mg/day orally, starting between days 2 and 4 of the cycle. The duration of NET therapy varied from 9 to 37 days. The mean time of onset of vaginal bleeding, after cessation of NET, was 2.9 +/- 0.7 days. Ovarian stimulation was carried out with a combination of a luteinizing hormone releasing hormone analog, follicle-stimulating hormone and human menopausal gonadotrophin. The day of human chorionic gonadotrophin (HCG) administration ranged from day 8 to day 15 of the cycle (10.1 +/- 1.7). On the day of HCG injection, the mean E2 level was 2188 +/- 1126. The mean number of follicles aspirated was 18.4 +/- 9.9 per cycle. The mean number of oocytes collected per cycle was 15.5 +/- 8.5. There was no correlation between duration of NET suppression and the number of days of gonadotrophin therapy needed to reach HCG administration. The large number of oocytes retrieved is probably related more with the fact that the patients represented a group with a purely male factor of infertility, than by the specific drug protocol utilized. Our results demonstrate that the ovarian response to gonadotrophin stimulation was not affected by NET administration. The main advantages of the use of this drug for cycle control are that its administration is oral, simple and inexpensive.

Adult↗

PubMed1990

A study of combined continuous ethinyl estradiol and norethindrone acetate for postmenopausal hormone replacement.

In a blinded, prospective, dose-response pilot study of continuous estrogen-progestin replacement therapy, 77 thin, nonsmoking, white women, who were 12 to 60 months postmenopausal and had normal medical histories, were randomly assigned to receive one of five dose combinations of daily ethinyl estradiol and norethindrone acetate (20 micrograms and 1.0 mg, 10 micrograms and 1.0 mg, 10 micrograms and 0.5 mg, 5 micrograms and 1.0 mg, and 5 micrograms and 0.5 mg) or conjugated estrogens 0.625 mg on days 1 to 25 and medroxyprogesterone acetate 10 mg on days 16 to 25. An additional 10 women meeting the same criteria served as a comparison group by taking calcium only. During 12 months of therapy, continuous users had significantly less vaginal bleeding and spotting than did sequential users. As compared with baseline values, bone metabolism and computerized tomographic measurements of vertebral trabecular bone density at month 12 indicated reduced bone turnover and increased density in hormone users. Endometrial biopsy specimens were negative for hyperplasia and neoplasia. The continuous ethinyl estradiol-norethindrone acetate tablet, even at the lowest doses studied, provided the same salutary effects on bone, endometrium, and postmenopausal symptoms as sequential therapy while minimizing annoying vaginal bleeding and spotting.

Adult↗

PubMed1994

Continuous combined and sequential estradiol and norethindrone acetate treatment of postmenopausal women: effect of plasma lipoproteins in a two-year placebo-controlled trial.

OBJECTIVE: Our purpose was to examine the effects of postmenopausal estrogen therapy supplemented with progestogen on plasma lipoprotein levels. STUDY DESIGN: One hundred thirteen women were randomized to receive either placebo or a combination of 17 beta-estradiol and norethindrone acetate administered continuously (Kliogest) or sequentially (Trisequens). Plasma lipoprotein levels were measured at baseline and after 2 years of treatment and compared by analysis of variance. RESULTS: Hormone therapy lowered plasma cholesterol levels (p < 0.001) and low-density lipoprotein cholesterol (Kiogest, p < 0.001; Trisequens, p < 0.01), whereas high-density lipoprotein cholesterol levels were unchanged (Trisequens) or reduced (Kliogest, p < 0.01), primarily because of a decrease in the high-density lipoprotein-2 subfraction (p < 0.05). Low-density lipoprotein/high-density lipoprotein cholesterol ratios remained unchanged. CONCLUSIONS: Although hormonal replacement therapy with estradiol combined with norethindrone acetate eliminated the increase in high-density lipoprotein cholesterol levels observed with estrogen monotherapy, the reductions in low-density lipoprotein cholesterol concentrations still suggest reduced cardiovascular risk, according to the National Cholesterol Education Program and to recent observations indicating that risk is not necessarily inversely proportional to high-density lipoprotein cholesterol levels.

Cholesterol↗

PubMed1994

A contraceptive vaginal ring releasing norethindrone acetate and ethinyl estradiol.

A core design contraceptive vaginal ring (CVR) releasing 650 mcg of norethindrone acetate (NA) and 10, 20, 30 or 65 mcg of ethinyl estradiol (EE) daily was developed and tested in 99 women. The CVR inhibited ovulation well with 30 or 65 mcg EE. Vaginal bleeding was better controlled than in 23 control women using NA/EE oral contraceptives. Side effects were comparable to controls for the 20 and 30 mcg EE CVR. The 65 mcg EE CVR resulted in an unacceptably high level of nausea. The 20 and 30 mcg EE CVR caused an increase in serum HDL cholesterol and triglycerides. Total cholesterol was unchanged. Angiotensinogen and sex hormone binding globulin-binding capacity were increased in a subgroup of the 20 and 30 mcg EE CVR subjects, similar to that of 20 controls using EE/gestodene oral contraceptives. This new CVR offers an excellent contraceptive alternative with the best performance provided by the 30 mcg EE dose.

Administration, Intravaginal↗