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Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone "add-back" therapy.

OBJECTIVE: To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis. DESIGN: Prospective randomized open label study. SETTING: Tertiary care university-affiliated reproductive medicine program. PATIENTS: Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis. INTERVENTIONS: All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III volunteers (n = 18) were untreated and followed for bone density changes. MAIN OUTCOME MEASURES: Disease extent at follow-up laparoscopy; pain, vasomotor, and vaginal symptom scores; bone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge. RESULTS: Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group III untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II. CONCLUSIONS: The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved.

Adult↗

The characterization of sulphated metabolites of norethindrone in human milk after oral administration of contraceptive steroids.

The excretion of ethynyl steroids in milk from a lactating woman taking a daily dose of an oral contraceptive (Conlumin) containing 1 mg of norethindrone and 50 micrograms of mestranol has been studied. Milk was diluted with aq. triethylamine sulphate and steroids were extracted on a Sep-Pak C18 cartridge at 60-64 degrees C. Groups of unconjugated steroids, glucuronides, mono- and disulphates were separated on triethylaminohydroxypropyl Sephadex LH-20. Following hydrolysis and further purification, steroids possessing an ethynyl-substituent were isolated by chromatography on sulphohydroxypropyl Sephadex LH-20 in silver form. Gas chromatographic-mass spectrometric analysis of the O-methyloxime-trimethylsilyl ether derivatives of these steroids, showed the presence of norethindrone and mestranol in the free fraction and of tetrahydro metabolites of norethindrone with 3 alpha,5 alpha, 3 alpha,5 beta and 3 beta,5 alpha configurations in the mono- and disulphate fractions. The disulphate of the 3 alpha,5 alpha isomer was the most abundant ethynyl steroid in milk after 13 days of administration. The site of conjugation of the monosulphates was established by acetylation prior to solvolysis and analysis by gas chromatography-mass spectrometry. This showed that the 3 alpha,5 alpha isomer was conjugated mainly in the 17 beta-position while the 3 alpha,5 beta isomer was conjugated at C-3.

Adult↗

Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy.

PURPOSE: Because enzyme-inducing antiepileptic drugs (AEDs) can affect pharmacokinetics of oral contraceptives and thereby cause contraceptive failure, the potential effect of topiramate, a new AED, on the pharmacokinetics of the combination oral contraceptive norethindrone/ethinyl estradiol was evaluated. METHODS: Twelve women receiving stable valproic acid (VPA) monotherapy for epilepsy received a combination norethindrone 1.0 mg/ethinyl estradiol 35-microg tablet daily for 21 days followed by seven daily doses of inert tablets for four 28-day cycles. After a baseline cycle (cycle 1), topiramate 100, 200, and 400 mg every 12 h was administered in cycles 2 through 4, respectively. Serial blood samples were obtained on day 20 of each cycle and were analyzed for norethindrone, ethinyl estradiol, and progesterone by using validated radioimmunoassay methods. RESULTS: Compared with cycle 1, none of the norethindrone pharmacokinetic parameters changed significantly in the presence of topiramate, 100-400 mg every 12 h. Individual patient serum progesterone concentrations measured during each cycle were at or close to the limit of quantification with no apparent differences among cycles. However, mean area under the concentration-versus-time curve over the 24-h period (AUC(0-24)) values for ethinyl estradiol were 18-30% lower in cycles 2 through 4 compared with cycle 1 (p < or = 0.05 for all pairs), whereas mean oral serum clearance (CL/F) values were 14.7-33.0% higher (p < or = 0.05 for cycles 2 and 4 vs. cycle 1). Mean time of peak concentration (T(max)) values determined during topiramate therapy were not significantly different from those at baseline. CONCLUSIONS: When prescribing an oral contraceptive for patients receiving topiramate, clinicians should consider initial therapy with an agent containing > or = 35 microg of ethinyl estradiol.

Adult↗

Effects of oral continuous and transdermal cyclic 17-beta estradiol and norethindrone acetate replacement therapy on platelet aggregation in postmenopausal women.

OBJECTIVE: To evaluate the effects of an oral continuous and transdermal cyclic 17-beta estradiol and norethindrone acetate combination on platelet aggregation in post-menopausal women. STUDY DESIGN: Fifty postmenopausal women were randomly assigned to receive 17-beta estradiol and norethindrone acetate either orally continuously or transdermally cyclically and sequentially. Platelet counts and maximum platelet aggregation rates were measured before and after three months treatment. RESULTS: At three months there were no significant changes in platelet counts or in adenosine diphosphate-induced or epinephrine-induced platelet aggregation rates in either treatment group. CONCLUSION: Hormone replacement treatment with a 17-beta estradiol and norethindrone acetate combination either orally continuously or transdermally cyclically and sequentially does not affect platelet aggregation in postmenopausal women.

Administration, Cutaneous↗

Riboflavin, self-report, and serum norethindrone. Comparison of their use as indicators of adolescent compliance with oral contraceptives.

The purpose of this study was to test the reliability of using the tablet marker, riboflavin, as an indicator of adolescent compliance with oral contraceptives, as compared with self-reports and more costly quantitative determinations of serum norethindrone levels. In a pilot study, a total of 31 urine samples were obtained from 11 subjects, aged 14 to 18 years. A follow-up study was conducted on 26 girls, aged 14 to 19 years, who were randomly selected from an ongoing study of oral contraceptive compliance. Subjects were given an oral contraceptive (Ortho-Novum 1/35), combined with 28 mg of riboflavin. In both studies, urinary fluorescence tests for riboflavin and self-reports were found to be significantly associated. In the follow-up study, both self-reports and urinary fluorescence tests were significantly associated with serum norethindrone levels. When the urinary fluorescence test agreed with self-report, compliance or noncompliance was confirmed by serum norethindrone levels in 90% of the cases. The findings suggest that riboflavin, combined with self-report, can be used as an accurate and cost-effective indicator of adolescent compliance with oral contraceptives.

Adolescent↗

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↗

An investigation of the effects of phenobarbitone on the pharmacokinetics of norethindrone in the rat using liver perfusion and everted gut sacs.

Previous in vivo studies have suggested that phenobarbitone increases the first pass clearance of norethindrone in the rat by induction of enzymes both in the gut wall and liver. In the present study phenobarbitone caused an increase in both the production of highly polar ether-extractable metabolites and the conjugation of the steroid as it crossed the wall of the everted gut sac preparation. In addition, there was a marked increase in the uptake of norethindrone into the liver followed by increased phase I metabolism in the isolated perfused liver. As expected for a highly cleared drug, enzyme induction had no measurable effect on the terminal half-life of norethindrone in the perfused liver preparation.

Animals↗

The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone.

BACKGROUND: Isotretinoin is a known teratogen, and when it is prescribed to women of childbearing potential, 2 forms of contraception must be used, commonly including hormonal contraception. Although isotretinoin and estradiol are metabolized largely by cytochrome P450 (CYP) 3A4 and glucuronidation, the potential for clinical drug interaction, with subsequent pharmacodynamic impact, has not been evaluated. METHODS: We enrolled 26 healthy women who were to receive isotretinoin for the treatment of severe, recalcitrant nodular acne and who were taking or planning to take oral contraceptives. The pharmacokinetics of ethinyl estradiol and norethindrone (INN, norethisterone) (the components of Ortho Novum 7/7/7; Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ) and pharmacodynamic assessments of oral contraceptive effectiveness (concentrations of serum progesterone, luteinizing hormone, and follicle-stimulating hormone) were determined on days 6 and 20 of 2 separate oral contraceptive cycles, before and during isotretinoin treatment. RESULTS: The addition of isotretinoin to the oral contraceptive regimen resulted in small and inconsistent, although statistically significant (P <.04), decreases in the concentrations of both ethinyl estradiol (9% decrease in area under the plasma concentration-time curve from time 0 to 24 hours after the dose on day 6) and norethindrone (11% decrease in maximum plasma concentration on day 20). Isotretinoin did not cause any statistically significant increases in pharmacodynamic markers, although a majority of women had increases in these measures. Although there was no correlation between isotretinoin (or metabolite) levels and oral contraceptive levels (P >.05), there was a correlation between progesterone level and oral contraceptive levels (P <.05). Variability was large for both pharmacokinetic measures (median coefficients of variation of 44%-69% [for each time point within a study period]) and pharmacodynamic measures (median coefficients of variation of 64%-114%). One woman in each study phase, one before and one during isotretinoin treatment, had a progesterone elevation consistent with possible ovulation. No serious or unexpected adverse events were observed. CONCLUSIONS: The small reduction in ethinyl estradiol and norethindrone levels associated with isotretinoin was not associated with any pharmacodynamic changes in our study. The combination of the teratogenic risk of isotretinoin and the large variability of and correlation between oral contraceptive levels and pharmacodynamic measures, however, strongly reinforces the necessity of additional contraceptive methods during concomitant administration of these drugs.

Acne Vulgaris↗

Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.

OBJECTIVES: This study evaluated the effect of the herbal remedy St. John's Wort on oral contraceptive (OC) therapy with respect to the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. METHODS: Sixteen healthy women were treated with a low-dose OC (Loestrin 1/20) and a placebo for two consecutive 28-day cycles in a single-blind sequential trial. Treatment with St John's Wort 300 mg three times daily was then added for two additional 28-day cycles. Outcomes compared between control and treatment cycles included the pharmacokinetics of norethindrone and ethinyl estradiol, daily bleeding diaries, follicle growth, changes in cervical mucus and progesterone levels drawn at 7- to 10-day intervals. RESULTS: Treatment with St. John's Wort was associated with a significant 13-15% reduction in the dose exposure from the contraceptive. Breakthrough bleeding increased in the treatment cycles, as did evidence of follicle growth and probable ovulation. CONCLUSION: St. John's Wort is associated with increased metabolism of norethindrone and ethinyl estradiol, breakthrough bleeding, follicle growth and ovulation. Women using OCs should be cautioned that St. John's Wort might interfere with contraceptive effectiveness.

Adult↗

Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, and 17beta-estradiol on vascular endothelial growth factor isomers 121 and 165 in Ishikawa cells.

OBJECTIVE: To determine the effect of 17beta-E(2), levonorgestrel, medroxyprogesterone acetate, and norethindrone on the expression of vascular endothelial growth factor (VEGF) isoforms 121 and 165 in Ishikawa cells in vitro. DESIGN: Prospective basic research study. SETTING: Basic research laboratory. PATIENT(S): None. INTERVENTION(S): Ishikawa cells were cultured in vitro. After 24 hours' incubation in serum-free media, 1.0, 0.1, and 0.01 microM concentrations of E(2), levonorgestrel, medroxyprogesterone acetate, and norethindrone were added for a further 24 hours of incubation. MAIN OUTCOME MEASURE(S): Isolation and identification of VEGF isoforms 121 and 165 using semiquantitative polymerase chain reaction, gel electrophoresis, with beta-actin as an internal control. RESULT(S): Estradiol stimulated VEGF isoforms 121 and 165. The progestins studied increased mRNA for VEGF isoforms 121 and 165 at all doses. Medroxyprogesterone acetate resulted in the greatest increase in both VEGF 121 and 165 compared with norethindrone and levonorgestrel. CONCLUSION(S): Estradiol and progestins increased VEGF 121 and 165 isoform mRNA in Ishikawa cells in vitro. We hypothesize that differences in VEGF expression may be associated with the irregular bleeding during progestin use in clinical situations.

Adenocarcinoma↗

Evaluation of genotoxic potential of synthetic progestins-norethindrone and norgestrel in human lymphocytes in vitro.

The genotoxicity study of two widely used contraceptive synthetic progestins, i.e. norgestrel and norethindrone was carried out on human lymphocyte chromosomes using chromosomal aberrations (CA), sister chromatid exchanges (SCE) and cell growth kinetics as parameters. The study was carried out both in the presence as well as in the absence of metabolic activation (S(9) mix). The lymphocytes were exposed to three different concentrations of the drugs (20, 40 and 75 microg/ml for norethindrone and 10, 25 and 50 microg/ml for norgestrel) for three different durations (24, 48 and 72 h). The drug norethindrone was found to be non-genotoxic at any concentration and at any exposure duration either in the presence or in the absence of S(9) mix. But another drug norgestrel was found to affect the genetic material. It induces CA, SCE at significant level, and inhibits lymphocyte proliferation at 25 and 50 microg/ml of concentrations only. In the presence of S(9) mix the values obtained for CA, SCE and mitotic index (MI) were more significant. A time and dose relationship was also observed. It was concluded that norgestrel itself and possibly its metabolites are potent mutagens beyond a particular dose in human lymphocytes.

Cell Cycle↗

Ethinyl estradiol and norethindrone in the treatment of primary hyperparathyroidism in postmenopausal women.

Treatment with ethinyl estradiol or norethindrone reduces the bone-turnover rate and plasma calcium levels in normal postmenopausal women, without affecting the secretion of calcium-regulating hormones. To assess the effect of these sex steroids in patients with primary hyperparathyroidism, we treated postmenopausal women who had hyperparathyroidism with either ethinyl estradiol (n = 6) or norethindrone (n = 11). After three weeks of treatment, the bone-turnover rate declined and plasma calcium fell from a mean (+/- 1 SE) of 2.77 +/- 0.07 mmol per liter (11.1 +/- 0.3 mg per deciliter) to 2.58 +/- 0.05 mmol per liter (10.3 +/- 0.2 mg per deciliter; P less than 0.01) in the group treated with ethinyl estradiol, and from 2.93 +/- 0.08 mmol per liter (11.7 +/- 0.3 mg per deciliter) to 2.84 +/- 0.08 mmol per liter (11.4 +/- 0.3 per deciliter; P less than 0.05) in the patients who received norethindrone. No significant changes in the plasma levels of parathyroid hormone, calcitonin, or calcitriol were observed after the estrogen-induced increases in vitamin D-binding protein had been taken into account. Since the decline in plasma calcium levels did not stimulate secretion of parathyroid hormone, we conclude that treatment with either sex steroid resets the threshold for secretion of parathyroid hormone. Thus, although the reductions in plasma calcium levels were moderate, sex-hormone therapy may be useful in the treatment of mild hyperparathyroidism in postmenopausal women.

Bone Resorption↗

Oral contraceptives, norethindrone and mestranol: effects on tissue levels of minerals.

The study involved three levels of dietary zinc (deficient, marginal, and adequate) and four hormonal conditions; namely, no steriods, norethindrone, mestranol, and norethindrone plus mestranol. The steroids were incorporated into diets and fed to 11-wk-old female Sprague-Dawley rats. After 10 wk of treatment, various tissues were excised for mineral assays by atomic-absorption spectrophotometry. Both steroids, reduced weight gain. Mestranol depressed plasma zinc, tibia copper and magnesium, and liver iron, but elevated the zinc levels in liver and erythrocytes, plasma copper, liver magnesium and calcium, and iron content of tibia and heart. In general, the effect was most prominent with adequate zinc but diminished in magnitude with the reduction of zinc intake. In addition, norethindrone increased heart iron and tibia calcium. Mestranol appeared to be the main causative factor and may have induced a possible shift of minerals from one pool to another. As expected, zinc deficiency resulted in the reduction of zinc concentrations of plasma, tibia, kidney, and pancreas, and the elevation of copper, iron, magnesium, and calcium concentrations of various tissues.

Animals↗

Norethindrone inhibition of testosterone secretion by an ovarian Sertoli-Leydig cell tumor.

A woman with severe hyperandrogenemia and virilization was found to have a fall in serum testosterone (T) concentration while taking an oral contraceptive containing norethindrone (500 vs. 164 ng/dL). Subsequent surgical exploration revealed an ovarian Sertoli-Leydig cell tumor. In vitro, the tumor secreted T (mean, 1.88 ng/mg X 4 h). hCG did not stimulate T secretion. In addition, norethindrone inhibited T secretion (0.33 ng/mg X 4 h). We conclude that norethindrone directly suppressed T production by the Sertoli-Leydig cell tumor.

Adult↗

[The efficacy and safety of domestic luteinizing hormone-releasing hormone analogue and low-dose norethindrone "add-back" therapy in the treatment of endometriosis].

OBJECTIVE: To study the efficacy and safety of combining domestic luteinizing hormone-releasing hormone analogue(LHRH-a) with low-dose norethindrone in the treatment of endometriosis. METHODS: Seventy-seven women with endometriosis were randomized into one of the following two groups. Group A (n = 36) were treated with LHRH-a (150 micrograms/d, i.m.) plus norethindrone (2.5 mg/d, p.o.) and group B (n = 41) received only LHRH-a (150 micrograms/d, i.m.) for 3 to 6 months. Symptoms and signs were recorded before and after the treatment. Liver and renal functions, lipid and bone metabolism and speed of sound (SOS) in the tibia were also examined at the same time. All data were analyzed using paired and grouped Student's t-tests. RESULTS: Total subjective symptom scores of group A showed 82% decrease at 3 months and 94% at 6 months of treatment (P < 0.01). Reductions in endometriotic foci were 34% and 61% at 3 and 6 months, respectively (P < 0.01). Of group B, there were 77% and 90% decreases in total subjective symptom scores at 3 and 6 months of treatment (P < 0.01). Reductions of 37% and 38% in endometriotic foci were observed at 3 and 6 months, respectively (P < 0.01). Liver and renal functions and fast blood sugar of both groups were all in normal range. Triglyceride (TG), apolipoproteinA (ApoA), serum calcium, phosphorus and alkaline phosphatase levels of group B increased significantly after treatment. And significant differences between the two groups were observed. There's no change of SOS in the tibia within or between the two groups before and after treatment. The percentages of hemorrhage in the group A and B were 18% and 38%, respectively. The percentages of hot flush and the other vasomotor symptoms were 14% and 41%, respectively (P < 0.01). CONCLUSIONS: Domestic LHRH-a combined with low-dose norethindrone was effective in the treatment of endometriosis. It could also improve the symptom of hypoestrogenemia, decrease hemorrhage rete and bone turn-over.

Adult↗

Cardiovascular risk factors during estrogen-norethindrone and cholecalciferol treatment.

The effect of cholecalciferol and estrogen-norethindrone treatment on total cholesterol level, high-density lipoprotein cholesterol level, blood pressure, and body mass index was investigated in 74 postmenopausal women in a double-blind, randomized trial. Blood pressure and body mass index did not change throughout the study. We demonstrated a decrease (11%) in serum cholesterol level after 1 year of treatment with estrogen-norethindrone. When this treatment was combined with cholecalciferol, a similar decrease (13%) was observed. The hypocholesterolemic effect was correlated to body mass index in a way that indicated the most pronounced decrease in lean women. The high-density lipoprotein cholesterol/total cholesterol fraction increased by 45% after 1 year of estrogen-norethindrone treatment, while an increase of 25% after 1 year was seen when cholecalciferol was added to the treatment. The latter increase was not different from a similar increase in the placebo group. The possible dyslipidemic effect of cholecalciferol, along with the risk of hypercalcemia, emphasizes the caution necessary in cholecalciferol treatment.

Aged↗

The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone.

Doxycycline and other antibiotics have been implicated in oral contraceptive (OC) failure, but information is sparse and studies of a doxycycline-OC interaction are nonexistent. Because an interaction between doxycycline and OCs, especially those containing low-dose estrogen, could result in an unplanned and unwanted pregnancy, a controlled clinical trial of the effects of doxycycline on OC hormone concentrations was performed. Twenty-four women aged 18-35 years were recruited as volunteers from among the patients seen in a University-based family planning clinic. While they were on a steady dose of the OC Ortho-Novum 1/35, serum concentrations of ethinyl estradiol, norethindrone, and endogenous progesterone were measured on days 18, 19, and 20 of the menstrual cycle (control phase). These measurements were repeated on days 18, 19, and 20 of the following menstrual cycle while the patient was taking doxycycline, 100 mg twice daily (treatment phase). No statistically significant differences in serum levels of ethinyl estradiol, norethindrone, or endogenous progesterone were seen between the control and treatment phases. However, there was large inter-patient and intra-patient variability in ethinyl estradiol and norethindrone levels. No elevations of endogenous progesterone occurred to suggest ovulation during antibiotic administration in either phase. It is not known what effects longer or earlier administration of doxycycline during the OC cycle would have on serum hormone concentrations or ovulation. Pregnancies attributed to failure of OCs because of tetracycline use could in fact be due to other causes or could represent a true interaction that only manifests itself in a small proportion of women at risk.

Adult↗

Treatment of postmenopausal hyperparathyroidism with norethindrone. Long-term effects on forearm mineral content.

In 15 postmenopausal women with mild primary hyperparathyroidism, the long-term effect of norethindrone therapy (5 mg/d) on forearm bone mineral content (FMC) was evaluated. The FMC rose from 810 +/- 39 (SEM) mg/cm at baseline to 841 +/- 41 mg/cm after 2 years of treatment, representing a mean bone mineral gain of 1.9% per year. The majority of this bone gain occurred during the first 6 months of treatment. The rate of increase in FMC in the first 6 months was +3.71 +/- 0.12 mg/cm per month compared with -0.35 +/- 0.51 mg/cm per month during the second year. Fat-corrected FMC was measured to determine whether the bone gain was real or reflected a decrease in fat mass. There was a similar rise in fat-corrected FMC (from 885 +/- 36 mg/cm at baseline to 909 +/- 39 mg/cm at 2 years). The difference between fat-corrected and uncorrected FMC, however, decreased slightly on norethindrone treatment (from 75.2 +/- 11.9 mg/cm at baseline to 67.8 +/- 11.8 mg/cm at 12 months), indicating a reduction in the subcutaneous fat layer. We conclude that norethindrone therapy in postmenopausal women with mild primary hyperparathyroidism produces a gain in bone mass that is sustained for at least 2 years.

Absorptiometry, Photon↗