***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Serum norethindrone ( NET ) ,  estradiol-17 beta ( E ) ,  progesterone ( P ) , and luteinizing hormone ( LH ) and follicle-stimulating hormone ( FSH ) levels were radioimmunoassayed in 15 women after injection of 300 mg  norethindrone enanthate ( NET-EN ) in 2 ml of oil ( 5 women ) , 200 mg NET-EN in 2 ml of oil ( 5 women ) , and 200 mg NET-EN in 1 ml of oil ( 5 women ) . These values were measured twice a week for 4 - 6 months to determine 1 ) the effect of various serum NET concentrations upon hypothalamic/pituitary-ovarian function ; 2 ) intersubject variability of this effect ; 3 ) between-subject variability of serum NET values ; 4 ) the effect of an increase in NET-EN dosage or in the volume of the vehicle ; and 5 ) the correlation between uterine bleeding and serum NET , E and P patterns . Peak serum NET levels were reached 4 - 15 days ( median 7 days ) postinjection . These high levels lasted about 20 days postinjection and then decreased , quickly at first and then gradually . Serum NET averaged 1.0 and .38 ng/ml 60 and 120 days postinjection and continued to be measurable in some of the subjects for up to a year . Calculations of day levels of serum NET revealed 63 % in the 1st 20 days , 26 % in the 2nd , and 11 % in the 3rd . Follicle development occurred between 33 - 116 days postinjection ( median 43 days ) and was followed by ovulation in only 1 subject ( 45 days postinjection ) with the 2nd earliest ovulation at 80 days postinjection . Uterine bleeding patterns were independent of dosage of NET-EN . The higher dose of NET-EN provides no contraceptive advantage , and the larger vehicle has no effect . A variability of positive feedback inhibition among subjects is thought to be responsible for differing patterns of return to ovulation , suggesting that for contraceptive purpose s a regimen of 150 mg or less NET-EN every 6 weeks may be appropriate A comparative study was undertaken in twenty-four Mexican women who discontinued the use of depo-medroxyprogesterone acetate ( DMPA ) or norethisterone enanthate ( NET-EN )  to assess the time required for the return to menses and ovulation . All subjects were exposed to long-acting injectable contraceptives for at least one year , and were followed prospect ively . Serum progesterone levels were determined weekly in all subjects beginning 3 months after the last progestogen injection . Mean time to return to ovulation occurred significantly earlier ( p less than 0.001 ) after NET-EN ( 2.6 months ) as compared with DMPA ( 5.5 months ) . No correlation between the return to ovarian function and the duration of steroid exposure was found . The overall data was interpreted as demonstrating a clear-cut difference between the two long-acting progestogens in terms of ovulation suppression The return of fertility following discontinuation of norethisterone oenanthate ( NET EN ) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy . Former users of copper intra-uterine device ( CuT 200 ) were enrolled as a control group . Another 161 women who had discontinued NET EN due to other reasons ( e.g. amenorrohea , excessive bleeding or personal reasons ) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy . The subjects from both groups were followed for a period of one year . The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant ( P greater than 0.05 ) . The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected . In 51 subjects who had discontinued NET EN  due to amenorrhoea , the return of fertility was predictably slower and less . The return of fertility in subjects who discontinued NET EN for other reasons ( e.g. excessive bleeding and other personal reasons ) was similar to ex-NET EN and ex-CuT 200 users Depo-Provera is a highly effective contraceptive , given intramuscularly ( 150 mg/mL ) once every 3 months . It has been in use in the United States for over 10 years . A new lower-dose formulation of Depo-Provera ( 104 mg/0.65 mL ) , has been developed that allows subcutaneous injection , potentially increasing the convenience , ease of administration and tolerability of this contraceptive . This prospect i ve , r and omized , single-center , single-dose trial evaluates the pharmacokinetics of the lower-dose formulation of Depo-Provera and compares the lower-dose formulation to the original formulation with regard to efficacy and duration of ovulation suppression and the return to ovulation at 12 months . While delivering a 30 % lower total dose than the intramuscular formulation , the lower-dose formulation of Depo-Provera  suppressed ovulation for more than 13 weeks in all subjects and was not affected by body mass index or race . Median time for return to ovulation was 30 weeks , with a 97.4 % cumulative rate of return to ovulation at 12 months BACKGROUND Progestin-only injectable contraceptives continue to gain in popularity , but uncertainty remains about pregnancy risk among women late for reinjection . The World Health Organization ( WHO ) recommends a " grace period " of 2 weeks after the scheduled 13-week reinjection . Beyond 2 weeks , however , many providers send late clients home to await menses . STUDY DESIGN A prospect i ve cohort study in Ug and a , Zimbabwe and Thail and followed users of depot-medroxyprogesterone acetate ( DMPA ) for up to 24 months . Users were tested for pregnancy at every reinjection , allowing analysis of pregnancy risk among late comers . RESULTS The analysis consists of 2290 participants contributing 13,608 DMPA intervals . The pregnancy risks per 100 women-years for " on time " [ 0.6 ; 95 % confidence interval ( CI ) , 0.33 - 0.92 ] , " 2-week grace " ( 0.0 ; 95 % CI , 0.0 - 1.88 ) and " 4-week grace " ( 0.4 ; 95 % CI , 0.01 - 2.29 ) injections were low and virtually identical . CONCLUSION Extending the current WHO grace period for DMPA reinjection from 2 to 4 weeks does not increase pregnancy risk and could increase contraceptive continuation A total of 2388 subjects , 1181 for 60 + /- 5-day and 1207 for 90 + /- 5-day treatment regimen with norethisterone oenanthate ( NET OEN ) 200 mg injection , were observed for 24 months , constituting 28,513 woman-months . This clinical trial represents the largest clinical trial undertaken on NET OEN . The observations indicated that NET OEN given at 60 + /- 5-day intervals provides adequate contraceptive protection . However , as compared to the published studies elsewhere , higher method failures were seen during the first six months of NET OEN usage , when all women were receiving the drug at 60 + /- 5-day intervals . The reasons for this discrepant observation in the present study can not be explained . The higher method failures reported with 90 + /- 5-day regimen were mainly during the third month following the injection , suggesting reduced contraceptive efficacy of the drug during this period . Thin build women ( body weight less than or equal to 40 kg ) were at higher risk of involuntary pregnancy . Disrupted menstrual pattern was the major reason for discontinuation ranging between 42 - 43 per 100 users at the end of 24 months . Amongst these , amenorrhoea was the commonest reason for discontinuation . No change in blood pressure was observed during contraceptive usage . The majority of NET OEN users did not show any change in body weight . The overall continuation rates with NET OEN were lower than those observed in similar conditions with Cu-T 200 mm2 IUCD BACKGROUND A new progestin-only , nondaily depot medroxyprogesterone acetate ( DMPA ) SC injectable contraceptive suspension ( 104 mg/0.65 mL ) has been developed . Clinical trials ( including dose-ranging , pharmacokinetic/pharmacodynamic , and contraceptive efficacy studies ) indicating the effectiveness of this new formulation were conducted primarily in white women . However , results of an early study by the World Health Organization suggested that in Thai women , medroxyprogesterone acetate ( MPA ) may be metabolized in < 91 + /- 7 days ( the range for effective suppression of ovulation established in clinical trials ) , result ing in a faster return to ovulation in this population . OBJECTIVES This study was design ed to determine the duration of ovulation suppression and investigate the pharmacokinetic profile of MPA after a single SC injection of DMPA 104 mg/0.65 mL in Asian women . It also assessed the effect of ethnicity and injection site on the duration of ovulation suppression . METHODS : This was a single-center , single-dose , open-label outpatient trial conducted in Singapore in Asian women aged 18 to 40 years . After 1 control cycle , women with confirmed ovulation were r and omized in a 1:1 ratio to receive an SC injection of DMPA 104 mg/0.65 mL in either the anterior thigh or the abdomen . Serum concentrations of MPA , progesterone , estradiol , luteinizing hormone , and follicle-stimulating hormone were measured during the 91-day dosing interval and for an additional 15 days thereafter . RESULTS Twenty-four Asian women ( mean [ SD ] age , 33.8 [ 43 ] years ; range , 22.7 - 40.1 years ; mean [ SD ] body mass index , 22.4 [ 3.0 ] kg/m(2 ) ) belonging to 5 ethnic groups ( Chinese , Filipino , Indian , Malaysian , and Thai ) were included in the study Ovulation suppression was maintained throughout the 91-day dosing interval , regardless of ethnicity or injection site . Ovulation was suppressed for at least 112 days after injection in 23 ( 95.8 % ) women , as evidence d by maintenance of serum progesterone concentrations < 4.7 ng/mL. The pharmacokinetic parameters for MPA in these Asian women were similar to those previously reported in white women . The most frequently reported adverse events were flulike symptoms and headache , all of mild to moderate intensity . No serious adverse events were reported . CONCLUSIONS In this study , SC DMPA 104 mg/0.65 mL provided effective suppression of ovulation for at least 91 days in Asian women . Ethnicity and injection site had no effect on MPA profiles Doses of DepoProvera of 25 , 50 , 100 and 150 mg were administered to four groups of women . The mean time for the return of follicular and luteal activity increased with increasing dose of DepoProvera .  Luteal activity was suppressed for a longer period than follicular activity . None of the women receiving the two higher doses of DepoProvera showed a return of luteal function within 100 days of injection . The period for which medroxyprogesterone acetate ( MPA ) was detectable in serum increased with increasing dose but the values for the 100 and 150 mg doses were not significantly different . There was a significant correlation between the concentration of MPA in blood and the return of follicular and luteal function . It is suggested that in the population studied , 100 mg DepoProvera would be as effective as the usual 150 mg dose and that injection of 50 mg DepoProvera would provide a contraceptive effect for two months . The dose of MPA in the monthly injectable CycloProvera could be substantially reduced without loss of effectiveness 
    Output:
    
Studies of return to ovulation after last injection of DMPA generally found that the earliest ovulation did not occur until several months after the last injection while studies of NET-EN reported ovulations around ( or even before ) the time for reinjection