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The plasma concentration of medroxyprogesterone acetate and ovarian function during treatment with medroxyprogesterone acetate in 5 and 10 mg doses.

Peripheral plasma levels of medroxyprogesterone acetate (MPA) were determined by radioimmunoassay in 5 women after oral administration of 5 and 10 mg medroxyprogesterone acetate daily. Peak levels of MPA in plasma were recorded within 1 - 3 hours of taking the tablet, which indicates a rapid absorption from the gastro-intestinal tract. The levels of medroxyprogesterone acetate 12 hours after taking of the 5 mg tablet remained constant throughout the 8 weeks of study. Peripheral plasma levels of estradiol and progesterone were determined throughout treatment. The estradiol levels indicated development of follicles in 7 out of 10 treatment months in the 5 mg group, and in 3 of the subjects treated with 10 mg MPA. The progesterone levels in those women treated with 5 mg MPA showed normal luteal concentration values in 2 out of 10 treatment months. No woman treated with 10 mg MPA had an increase in progesterone during the 21-day period of treatment. The results obtained in this study suggest that 10 mg MPA daily will inhibit ovulation but 5 mg is not sufficient to inhibit ovulation in all women.

Administration, Oral↗

Serum medroxyprogesterone acetate levels in new and repeat users of depot medroxyprogesterone acetate at the end of the dosing interval.

In the absence of published data on serum medroxyprogesterone acetate (MPA) levels in South African users, this study examines such levels in new and repeat users of depot medroxyprogesterone acetate at the end of the dosing interval. The study was undertaken at three family-planning clinics in Durban, South Africa. Serum MPA levels were measured in 94 Black African, Indian and White women returning between 11 and 14 weeks after their last injection. The median serum MPA level was 0.88 (range, <0.04-1.77) ng/mL and wide interindividual variability was observed. Levels in all but one woman were higher than 0.1 ng/mL, the level at which ovulation is reported to resume. MPA levels were not found to vary according to weight, body mass index or ethnicity. Although there was a slight tendency towards higher MPA levels with longer duration of use (r = 0.13), the wide interindividual variability precluded the possibility of determining whether this was a real trend. A prospective study, using standardized assay techniques and following individual women, is required to further clarify this issue.

Adolescent↗

Teratogenic effects of cyproterone acetate and medroxyprogesterone treatment during the pre- and postimplantation period of mouse embryos. II. Cyproterone acetate and medroxyprogesterone acetate treatment before implantation in vivo and in vitro.

The study was performed to investigate direct embryotoxic effects of maternal progestin treatment during the preimplantation period. In the first experiment pregnant mice received a single subcutaneous injection of either cyproterone acetate (CA) or medroxyprogesterone acetate (MPA) on day 2 of pregnancy (5-600 mg/kg). In a second experiment four-cell embryos were exposed to CA or MPA in vitro (3 or 30 micrograms/ml medium). Our results revealed: (1) After maternal treatment the number of live embryos was reduced after the highest CA dose. Development into blastocysts was inhibited in a dose-related manner after CA but not after MPA. The number of cells in morulae, blastocysts, and of the inner cell mass (ICM) of late blastocysts was not affected. (2) When morulae and blastocysts were cultured in vitro after maternal treatment, hatching, attachment, and trophoblast outgrowth were inhibited after high doses, but development and differentiation of the ICM were inhibited even after low doses. (3) Application of 30 micrograms/ml of CA or MPA in vitro was directly embryolethal. Three micrograms/ml did not affect development into blastocysts, but ICM development and differentiation were again inhibited during subsequent culture in hormone-free medium. (4) Qualitative protein synthesis was altered in morulae and blastocysts 24 hours after maternal CA treatment. According to our results high doses of progestins are embryotoxic before implantation, low doses have delayed effects on embryonic development that are particularly evident after implantation in vitro.

Animals↗

Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67.

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy. In meningioma specimens from patients receiving no MPA therapy, Ki-67-positive cells were present in 1.02 +/- 0.48%; in samples from MPA-treated tumors the percentage of Ki-67-positive cells was 0.41 +/- 0.40 (different at p less than 0.02 [Wilcoxon's test]). In comparison to our previously published data on untreated meningiomas analyzed for progesterone receptors (PR), MPA significantly reduced the PR activity. There was no obvious correlation between PR activity and potential suppression of the tumor growth fraction. It is concluded that MPA is attractive because it reduces the growth fractions of most meningiomas and might be suitable for adjuvant hormonotherapy.

Antibodies, Monoclonal↗

Angiogenic activity of rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene and its inhibition by medroxyprogesterone acetate: possible involvement of antiangiogenic action of medroxyprogesterone acetate in its tumor growth inhibition.

The significant inhibitory activity of medroxyprogesterone acetate (MPA) against mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was confirmed in female Sprague-Dawley (SD) rats, and was found to be independent of the estrogen receptor (ER) level. To facilitate elucidation of the mechanism underlying the antitumor activity of MPA against the rat mammary tumors (RMTs) regardless of ER status, the present study was conducted to determine whether or not a DMBA-induced RMT had the capacity to elicit angiogenic activity on tissue implantation into a rabbit cornea, and, if so, to determine whether or not the angiogenic activity of the RMT was inhibited by MPA. The RMTs obtained were classified into two groups based on the ER level; ER-positive and -negative groups. Both groups exhibited relatively strong angiogenic activity, the activity of the ER-negative group being significantly higher than that of the ER-positive one. The angiogenesis produced by both groups of RMTs was significantly inhibited by MPA, as judged from the results of the rabbit cornea assay. Similarly, MPA almost entirely suppressed not only the angiogenesis but also the growth of rabbit VX2 tumors without ER, included as a positive control as to the induction of angiogenic activity. In vitro experiments using neoplastic epithelioid RMT-1 and -2 cells cloned from DMBA-induced RMTs demonstrated that MPA had little or no suppressive effect on the growth of these epithelial cells. These results suggest that the inhibitory action of MPA toward the angiogenic activity of RMTs, at least in part, involves its antitumor activity toward the RMTs.

9,10-Dimethyl-1,2-benzanthracene↗

[The medroxyprogesterone acetate serum level following various medroxyprogesterone acetate dose schedules in gynecologic oncology].

Medroxyprogesterone acetate (MPA) is used as an adjuvant hormonal medication in patients with different kinds of carcinomas. Since adequate serum levels are thought to be essential we determined the individual, postoperative MPA levels in 36 patients with endometrial carcinoma over a period of 12 weeks. The patients received either an oral dose of 3 X 100 mg MPA or a weekly changing scheme with 2 X 10 mg Tamoxifen and 3 X 100 mg MPA. An additional small group of 4 patients with ovarian carcinoma was enrolled receiving an oral dose of 1000 mg MPA daily. The peripheral serum levels of MPA exhibit enormous inter- and intraindividuell variations and only the high dosage schemes yield levels above 90 ng/ml which are claimed necessary by some authors. The cortisol concentration measured at the same time were within the normal range and did not correlate with the MPA values.

Antineoplastic Agents↗

Depot medroxyprogesterone acetate use in inner-city, minority adolescents: continuation rates and characteristics of long-term users.

OBJECTIVE: To identify continuation rates of depot medroxyprogesterone acetate (Depo-Provera) and characteristics of long-term users in a population of inner-city, minority adolescents with high pregnancy rates. DESIGN: Retrospective medical record review. SETTING: An inner-city adolescent clinic and an adolescent pregnancy program. METHODS: A review of the medical records of 250 females aged 13 to 20 years (mean +/- SD, 16.8 +/- 1.1 years), 62.9% Hispanic and 34.2% African American, receiving a first depot medroxyprogesterone acetate injection for contraception between August 1993 and June 1996 was conducted using a standardized form. The mean +/- SD age at menarche of the subjects was 11.6 +/- 1.4 years, and the mean +/- SD age at first intercourse was 14.1 +/- 1.3 years; the mean number of lifetime sex partners was 2.4. Of the subjects, 73.6% had used condoms, 32.0% used oral contraceptives, and none used implants. Of the 201 subjects for whom there were data in the medical records regarding prior fertility, 172 (85.6%) had been pregnant, and 145 (72.1%) had a child. Life table analysis was used to measure depot medroxyprogesterone acetate continuation rates and to compare subgroups of adolescents. RESULTS: Depot medroxyprogesterone acetate continuation rates were found to be 70.3% at 6 months, 48.3% at 9 months, 31.5% at 12 months, and 12.8% at 24 months. The most common reason for depot medroxyprogesterone acetate discontinuation was missed appointments (41.7%). Subjects were followed up for a mean +/- SD of 1.3 +/- 0.7 years after discontinuation of depot medroxyprogesterone acetate use; 46.7% became pregnant. Among those 156 adolescents who discontinued depotmedroxyprogesterone acetate use, 40.0% restarted the method at some later time. Continuation of depot medroxyprogesterone acetate use was more likely if age at first intercourse was younger than 13 years (P = .04). Continuation rates were not related to age, ethnicity, age at menarche, number of sex partners, use of other contraceptives, prior pregnancy, or having a child. CONCLUSIONS: In this study, just less than one third of the adolescents continued depot medroxyprogesterone acetate use for 1 year or longer. This suggests that depot medroxyprogesterone acetate does not function as a long-term method for most inner-city adolescents. The only characteristic that was associated with successful continuation of depot medroxyprogesterone acetate use was young age at first intercourse, implying that experience may be the main determinant of continuation.

Adolescent↗

Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances.

OBJECTIVE: Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances. The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern, using treatment with cyclic medroxyprogesterone, with or without calcium supplementation, in physically active women with disturbed menstruation. DESIGN: This study was a 1-year randomized, double-blind, placebo-controlled trial. Women who were stratified by menstrual cycle disturbance were randomized into four groups. The outcome variable was the change in spinal bone density measured by dual energy techniques. SETTING: A large metropolitan area. PARTICIPANTS: Sixty-one healthy, normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea, oligomenorrhea, anovulation, or short luteal phase cycles completed the study. INTERVENTION: Therapies were cyclic medroxyprogesterone (10 mg/day for 10 days per month) and calcium carbonate (1,000 mg/day of calcium) in four groups: (A) (n = 16) cyclic medroxyprogesterone plus calcium carbonate; (B) (n = 16) cyclic medroxyprogesterone with calcium placebo; (C) (n = 15) placebo medroxyprogesterone with active calcium; or (D) (n = 14) both medroxyprogesterone and calcium placebos. RESULTS: The initial bone density (mean = 1.12 g/cm2) did not differ by group (P = 0.85). The 1-year bone density change was strongly related to treatment with medroxyprogesterone (P = 0.0001) and weakly to calcium (P = 0.072) treatment. Bone density increased significantly (+1.7% +/- 0.5%, +/- SEM, P = 0.004) in the medroxyprogesterone-treated groups (A and B), did not change in the calcium-treated group (C) (-0.7% +/- 0.6%, P = 0.28), and decreased on both placebos (D) (-2.0% +/- 0.6%, P = 0.005). CONCLUSIONS: Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances. POTENTIAL CLINICAL SIGNIFICANCE: Amenorrhea, oligomenorrhea, anovulation, and short luteal phase cycles are common in premenopausal women and associated with spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing. This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group, whereas those subjects in the placebo group lost bone. Calcium supplementation appeared to be helpful but did not reach statistical significance. The implications of these findings for the prevention of osteoporosis warrant further investigation.

Adult↗

The effect of medroxyprogesterone acetate and heparin in the prevention of postsurgical adhesion formation in the rat uterine model.

OBJECTIVE: To evaluate the effects of depot medroxyprogesterone acetate and heparin in preventing postsurgical adhesion formation in the rat model. METHODS: A hundred and five female Wistar rats were divided into 7 groups. Groups 1 and 2 were injected with intramuscular 15 mg medroxyprogesterone acetate 3 weeks before surgery and at the end of laparotomy. Groups 3 and 4 were given 15 mg medroxyprogesterone acetate by intramuscular injection, 3 weeks before surgery. An equal volume of intramuscular sterile saline was injected to control groups, 3 weeks before and at the end of surgery. Before abdominal closure, 2 ml of Ringer's lactate was instilled into the peritoneal cavity of all rats, except group 7. Groups 1, 4, and 5 were given 2 ml of intraperitoneal Ringer's lactate containing 500 U heparin/ml. A standardized surgical injury was performed in all rats. Two weeks after surgery, the adhesions were scored on a scale of 0 to 3 according to their thickness-tenacity and vascularity. Kruskall-Wallis and Mann-Whitney U statistical test were used. RESULTS: The preoperative and postoperative administration of medroxyprogesterone acetate resulted in the least number of and the least severe adhesions, when compared with single dose medroxyprogesterone acetate treated rats and controls (p < 0.05). However, the combination of medroxyprogesterone acetate and intraperitoneal heparin did not enhance the adhesion reducing capacity of medroxyprogesterone acetate. CONCLUSIONS: Concurrent preoperative and postoperative administration of medroxyprogesterone acetate results in the most significant reduction of postsurgical adhesions. The combination treatment of medroxyprogesterone acetate and heparin does not show any additional effect in the reduction of adhesion formation, when compared with medroxyprogesterone acetate treatment alone.

Animals↗

Randomized phase II study comparing thalidomide with medroxyprogesterone acetate in patients with metastatic renal cell carcinoma.

PURPOSE: To investigate escalating doses of thalidomide compared with medroxyprogesterone in patients with metastatic renal cell carcinoma (RCC), who had either progressed after first-line immunotherapy or who were not suitable for immunotherapy. PATIENTS AND METHODS: Thalidomide was started at 100 mg/d orally (PO) and escalated by 100 mg/d every 2 weeks to the maximum dose of 400 mg/d. Medroxyprogesterone was given at a fixed dose of 300 mg PO daily. RESULTS: Sixty patients were entered (thalidomide:medroxyprogesterone = 29:31; median age, 59 [thalidomide], 60 [medroxyprogesterone]; No. of patients assessable for response, 22 [thalidomide], 26 [medroxyprogesterone]). In the thalidomide arm, there was no objective response seen. The best response was SD in three patients lasting 5+, 6+, and 12 months, respectively. All patients in the medroxyprogesterone arm progressed. There was no difference in overall survival between the two arms; median survival in the thalidomide arm was 8.2 months compared with 4.8 months in the medroxyprogesterone arm (P = .62). Hazard ratio was 0.88 (95% CI, 0.67 to 1.94). Median duration of treatment was 73 days (range, 14 to 364 days) in the thalidomide arm, and 84 days (range, 7 to 175 days) in the medroxyprogesterone arm. The high incidence of toxicity in the thalidomide arm, mainly somnolence, constipation, fatigue and paraesthesia, meant that only 30.8% of patients were able to tolerate the maximum dose of 400 mg/d of treatment. CONCLUSION: Thalidomide is not superior to medroxyprogesterone acetate in patients with metastatic RCC. Its risk/benefit ratio does not favor its use in this patient population.

Adult↗

Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women.

Thirty-five women who had undergone a natural or surgical menopause were randomized to receive either 0.625 mg of conjugated estrogen to be ingested for 25 days each month or 150 mg of depo-medroxyprogesterone acetate intramuscularly every three months. Plasma lipids were determined before and after one year of therapy. Serum androgens were measured before and after six months of therapy. Conjugated estrogens and depo-medroxyprogesterone acetate had similar effects on plasma lipids. Cholesterol was decreased (P less than .02 for conjugated estrogen therapy and P less than .01 for depo-medroxyprogesterone acetate therapy), as was low-density lipoprotein cholesterol (P less than .02 for conjugated estrogen and P less than .05 for depo-medroxyprogesterone acetate). Conjugated estrogens also significantly increased high-density lipoprotein cholesterol (P less than .02). High-density lipoprotein cholesterol levels were unchanged after depo-medroxyprogesterone acetate therapy. Serum androgens were generally unchanged after depo-medroxyprogesterone acetate or conjugated estrogen therapy. The data from this study suggest that long-term conjugated estrogen and depo-medroxyprogesterone acetate treatment have similar effects on lipid and androgen levels except that high-density lipoprotein cholesterol was not significantly increased by depo-medroxyprogesterone acetate.

Adult↗

A double-blind randomised controlled trial of the effects of medroxyprogesterone acetate on bone density of women taking oestrogen replacement therapy.

OBJECTIVE: To assess the effects of medroxyprogesterone acetate on bone density in women who have had a hysterectomy. DESIGN: Randomised, double-blind, placebo-controlled trial of medroxyprogesterone acetate 10 mg, 20 mg or placebo as an adjunct to oestrogen therapy. PARTICIPANTS: One hundred and twenty-three women, aged 18 to 45 years and currently receiving daily oestrogen, who presented at a university-based rheumatology practice. INTERVENTIONS: The women were randomly assigned to receive either medroxyprogesterone acetate 10 mg, 20 mg or placebo daily beginning on day 15 of each month for one year. Forty-one women were randomised into each group. MAIN OUTCOME MEASURE: The primary outcome measurement was the percentage of change from baseline in bone mineral density of the lumbar spine (L2-L4). Secondary outcome measures included differences in femoral neck bone density, cholesterol and triglyceride levels between groups. RESULTS: At one year, change in bone mineral density did not differ between either the treatment or placebo groups. Medroxyprogesterone acetate 20 mg and 10 mg led to statistically significant reductions in very low density lipoprotein cholesterol, total triglycerides, and very low density lipoprotein triglycerides when compared with placebo. Medroxyprogesterone acetate 20 mg also led to a statistically significant reduction in high density lipoprotein cholesterol, high density lipoprotein-2 cholesterol, and high density lipoprotein-2 triglycerides. CONCLUSIONS: Medroxyprogesterone acetate at either dose as an adjunct to oestrogen did not improve bone mineral density at one year when compared with placebo. Medroxyprogesterone acetate 10 mg may not adversely affect lipids. Medroxyprogesterone acetate 20 mg, however, did reduce high density lipoprotein cholesterol and therefore may increase cardiovascular risk.

Adolescent↗

Medroxyprogesterone at high altitude. The effects on blood gases, cerebral regional oxygenation, and acute mountain sickness.

OBJECTIVE: To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude, alone and in conjunction with acetazolamide, and to assess the effect on acute mountain sickness (AMS). DESIGN: Two placebo-controlled trials during rapid ascent to high altitude. PARTICIPANTS: In the first trial, 20 participants, and in the second trial, 24 participants. SETTING: During rapid ascent to 4680 m and on rapid ascent to 5200 m. INTERVENTION: In the first trial, participants were randomized to receive medroxyprogesterone 30 mg or a placebo twice a day. In the second trial, participants were randomly assigned to one of 4 groups: a placebo twice daily, medroxyprogesterone 30 mg twice daily, acetazolamide 250 mg plus a placebo twice daily, or acetazolamide 250 mg plus medroxyprogesterone 30 mg twice daily. MAIN OUTCOME MEASURES: Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only. RESULTS: Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved PaO2 in combination with acetazolamide. Cerebral regional oxygen saturation was not altered by medroxyprogesterone. The reduction in symptom scores and in the extent of AMS was not significant in this limited study. CONCLUSIONS: Medroxyprogesterone acts as a respiratory stimulant, but the clinical benefit regarding the development of AMS was unproven at high altitude. Combined medroxyprogesterone and acetazolamide gave the best PaO2.

Acetazolamide↗

The effect of medroxyprogesterone acetate on premature labor in the sheep.

The ability of medroxyprogesterone acetate to delay premature delivery was investigated in nine chronically catheterized pregnant sheep (125 to 130 days' gestation). Catheters were placed for measurement of intrauterine pressure and uterine vein concentrations of progesterone, 17 beta-estradiol, and 15-keto-13,14-dihydroxyprostaglandin F2a. Premature parturition was induced in all animals by infusion of dexamethasone (1 mg/24 hours) to the fetus. Three ewes served as controls, three ewes received oral medroxyprogesterone acetate (5 mg/kg/day) 48 hours prior to the start of and during dexamethasone (early medroxyprogesterone acetate), and the remaining three animals received oral medroxyprogesterone acetate 12 hours after the onset of dexamethasone infusion (late medroxyprogesterone acetate). The lengths of time from dexamethasone until the onset of labor and from dexamethasone until delivery were compared, and were significantly longer for each group compared to control times. Of all endocrine events analyzed, the fall in plasma progesterone was the most consistent in all groups, showing that animals with rapid falls in progesterone levels (control group) tended to deliver earlier. These results demonstrate that medroxyprogesterone acetate can delay premature parturition in the sheep. Also medroxyprogesterone acetate appears to delay the endocrinologic events that normally occur at this time.

Animals↗

Comparison of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep in patients with chronic obstructive lung disease.

The effects of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep were compared in six patients with chronic obstructive lung disease and carbon dioxide retention. Patients received 1.5 mg/kg almitrine (a peripheral chemoreceptor stimulant), 100 mg of medroxyprogesterone (a central respiratory stimulant), or matched placebo daily for 15 days in random order in a crossover trial. When subjects were awake almitrine increased the ventilatory response to hypoxia and increased arterial oxygen tension (PaO2) to a greater extent than medroxyprogesterone, whereas medroxyprogesterone augmented the ventilatory response to hypercapnia and decreased arterial carbon dioxide tension (PaCO2) to a greater extent than almitrine. Neither drug influenced sleep architecture significantly, except that medroxyprogesterone increased the number of arousals. Almitrine had a more favourable effect than placebo on oxygenation as estimated from arterial oxygen saturation (SaO2) during the different stages of sleep, the number of episodes of hypoxaemia, and the amount of time that SaO2 was below 80%. The only change with medroxyprogesterone by comparison with placebo was a decrease in the number of hypoxaemic episodes. It is concluded that both active drugs improved blood gases during wakefulness, but that 1.5 mg/kg of almitrine is superior to 100 mg of medroxyprogesterone in improving SaO2 during sleep.

Almitrine↗

Genotoxic potential of medroxyprogesterone acetate in cultured human peripheral blood lymphocytes.

Medroxyprogesterone acetate was studied at three different concentrations (1, 5 and 10 microM), for its genotoxic effects in human peripheral blood lymphocyte culture using chromosomal aberrations and sister chromatid exchanges as parameters. Duplicate peripheral blood cultures were treated with three different concentrations (1, 5 and 10 microM) of medroxyprogesterone acetate. The study was carried out both in the absence as well as in the presence of metabolic activation (S9 mix) with and without NADP. Medroxyprogesterone acetate was found genotoxic at 5 and 10 microM in the presence of S9 mix with NADP. To study the possible mechanism of the genotoxicity of medroxyprogesterone acetate, superoxide dismutase and catalase at different doses were used separately and in combination with 10 microM of medroxyprogesterone at different doses in the presence of S9 mix with NADP. Superoxide dismutase treatment results in an increase of the genotoxic damage but catalase treatment reduce the genotoxic damage of medroxyprogesterone acetate. Catalase treatment in combination with superoxide dismutase also results in the further reduction of the genotoxic damage. The results of the present study reveal that medroxyprogesterone acetate is genotoxic only in the presence of metabolic activation (S9 mix) with NADP. Treatments with superoxide dismutase and catalase suggests the possible generation of reactive oxygen species by redox cycling of various forms of quinones, similar to estrogens, that are the results of aromatic hydroxylation by cytochrome P450s.

Antioxidants↗

Spinal bone density in women using depot medroxyprogesterone contraception.

OBJECTIVE: To determine factors possibly associated with reduced bone density in women using the injectable contraceptive depot medroxyprogesterone acetate. METHODS: In a cross-sectional study, bone mineral density of the lumbar spine was measured by dual energy x-ray absorptiometry in 200 current users of depot medroxyprogesterone acetate who had used this method of contraception for 2-26 years and compared with 350 control subjects. Bone density results are expressed as standard deviation scores (z score). RESULTS: The bone density was significantly lower in depot medroxyprogesterone acetate users (mean z score: -0.65, 95% confidence intervals [CI] -0.80, -0.49, P < .001). Bone density was significantly reduced in nonsmokers and smokers, and there was no significant difference in mean z score between smokers and nonsmokers (mean -0.75 versus -0.58, P=.30). Women who had started depot medroxyprogesterone acetate after the age of 20 years and who had used it for 15 or fewer years had a significantly higher bone density than the remainder of the cohort (mean -0.45 [95% CI -0.62, -0.27] versus -1.02 [95% CI -1.32, -0.73], P < .005). Bone density in depot medroxyprogesterone acetate users was not related to current age, parity, body mass index, calcium intake, or exercise. CONCLUSION: Depot medroxyprogesterone acetate use is associated with a significant reduction in bone density, and although a high proportion of depot medroxyprogesterone users do smoke, the reduction in bone density cannot be explained by smoking. Women who use it for a long time and those who start it before peak bone mass is attained may be at highest risk.

Adolescent↗