- Email: [email protected]
Depression in users of depo-medroxyprogesterone acetate
ELSEVIER
Depression in Users of Depo-Medroxyprogesterone
Acetate
Carolyn Westhoff, Daryl Wieland,* and Lorraine Tiezzi Prevalence of depression is high among poor, young, Hispanic inner city women. Depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in this group. DMPA labelling suggests that depression may worsen with use. In order to identify any association of DMPA use with worsening depression, we surveyed an English-speaking subset of DMPA users in a Title-X funded family planning clinic. Eighty women completed the CES-D scale on two occasions: once about four weeks after a DMPA injection when the subject would have been exposed to the highest blood levels, and once immediately prior to an injection when recent blood levels of the drug would be somewhat lower (or absent preceding the first injection). The median CES-D score was 14. The scores were not related to timing of the test (pre- or postinjection). The depression scores were somewhat higher among those women receiving their first DMPA injection during the study period (i.e., unexposed women) and among those women who had received four or more injections. Scores were unrelated to age or parity, but were somewhat higher in women who reported fewer years of education or a recent adverse pregnancy outcome. These data provide little evidence of increasing depression with long-term use of DMPA and no evidence of a short-term effect of dose (within the contraceptive range) on mood. Women at risk of depression should not be denied DMPA as a contraceptive choice. CONTRACEPTION 1995;51:351354 KEY WORDS: depression, contraception,
progesterone
Introduction epot-medroxyprogesterone acetate (DMPA) was approved by the FDA for contraceptive use in November 1992. In the precaution section, the package labelling states that “patients who
D
Columbia University School of Public Health and College of Physicians and Surgeons, New York, NY and ‘Department of Obstetrics and Gynecology, Mt. Sinai Medical Center, New York, NY Name and address for correspondence: C. Westhoff, MD, Department of Obstetrics and Gynecology, Columbia University, 630 West 168 St., New York, N.Y. 10032. Tel: (212) 305-7070; Fax (212) 305-3869 Submitted for publication November 15, 1994 Revised April 11, 1995 Accepted for publication April 11, 1995
0 1995 Elsevier Science Inc. 655 Avenue of the Americas, New York,
NY 10010
have a history of psychic depression should be carefully observed and the drug not be readministered if the depression recurs.” This precaution was based on clinical data submitted to the FDA showing that 1.5% of 4200 users reported depression and 0.5% discontinued use of DMPA for this reason.’ The individuals who use the Columbia-Presbyterian Medical Center Family Planning Clinics are predominantly young, poor, urban, Hispanic females; these characteristics are associated with a high prevalence of depression.2 Substantiating this, in the last six months of 1994, 87 patients attending these clinics were referred to psychiatry for evaluation and treatment of depression. Since its approval by the FDA, DMPA has become a popular contraceptive choice in this population. The purpose of this study was to identify whether some aspects of DMPA use are associated with depressive symptoms in this high risk population.
Methods The study sample was selected from all patients at the Columbia-Presbyterian Medical Center Family Planning Clinics who were DMPA users during December 1993 and January 1994. All of their medical records were abstracted for routinely collected data including age, race, preferred language, years of education, pregnancy history, and the dates of all DMPA injections. English-speaking or bilingual subjects who sought a first or subsequent DMPA injection in the clinic during these months were invited into this IF&approved study by a single clinician (DW). If a DMPA user was seen by another clinician, she was not invited to participate in the study. Participation consisted of completing a brief set of questions about mood during the previous week on two occasions about two months apart. The questions were completed either in person or over the telephone. In addition, a group of Englishspeaking patients who were not using DMPA were asked to complete the interview once. The Community Epidemiology Survey-Depression Scale (CES-D) was used to assess depressive symptoms.3 This short self-report scale is designed to ISSN OOlO-7824/95/$9.50 SSDI OOl O-7824(95)00100-O
352
Contraception 1995;51:351-354
Westhoff et al.
measure depressive symptoms during the previous week in the general population; this scale has been extensively validated and widely used in population studies of depressive symptoms. The possible scores range from 0 to 60, and a score of 16 or greater is frequently used as a threshold suggesting risk of clinical depression; however, this threshold has poor specificity and is not appropriate in all populations.2 For adolescent females, a score of 22 or greater may be a more appropriate threshold. The timing of the two questionnaires for each DMPA user was intended to correspond to intervals of relatively high and low exposure.4 The high exposure week was one month after an injection of DMPA. The low exposure week was immediately before the first injection or before a scheduled reinjection. Because subjects might report fewer symptoms and thus have a systematically lower score on the second test,5 the order of the tests was alternated so that some subjects were first tested after the high exposure week and others were first tested after the low exposure week. Baseline characteristics of the study subjects were compared to the baseline characteristics of all DMPA users. The main outcome of interest was whether the CES-D scores were related to the level of DMPA exposure (“high” versus “low”) or to the duration of use of DMPA as measured by the total number of injections received. The association between CES-D scores and baseline characteristics was assessed in order to identify whether expected associations were seen in the study population. These variables as well as test order and test method (in person versus by telephone) were assessed to identify and adjust for any confounding effect on the main associations. The CES-D scores were right skewed; however, transformations performed to normalize the distribution had no important effect on any of the associations considered. The scores that are presented are untransformed. T-tests, paired and unpaired, and analysis of variance were used to compare mean CES-D scores between subjects. The proportion of scores falling above the thresholds of 16 and 22 points in subgroups of sub-
jects were compared using a &i-square tinuity correction.
test with con-
Results Three-hundred-seventy-nine DMPA users were identified by record review during December 1993 and January 1994. Eighty-two DMPA users were invited to participate in the studyj two were lost to follow-up after the first test. Twenty-six consecutive Englishspeaking non-DMPA users were also interviewed during a single clinic visit. No women refused to participate. Age and parity were similar between the 80 study subjects who completed two CES-D tests and all 379 DMPA users (Table 1). The study subjects reported slightly more years of school (p = 0.04). This is likely to have occurred because speaking and reading English was a requirement for participation in the study. Only 39 subjects considered English to be their first language, but CES-D scores were not related to whether the first language was English or Spanish. Seventy-one of the subjects were Hispanic, and most of these were Dominican; the remaining nine subjects were black. The CES-D scores in this sample were unrelated to ethnicity. The overall mean CES-D score in the DMPA users was 15.6 with a range from 0 to 37 points. The characteristics of the 26 English-speaking DMPA non-users who were interviewed are also shown in Table 1. Their mean CES-D score was 14.4 with a range from 0 to 38 points. Overall, this small group of non-users attending the same clinic was similar to the DMPA users for these characteristics. In the full group of DMPA users there were 73 women whose last injection had been given more than 100 days before the medical record was abstracted. These women were presumed to be discontinuing the method; their age, parity, and education was similar to the continuing users, but they had fewer injections than the continuing users which includes the study subjects. Table 2 shows that there was no evidence of more
Table 1. Baseline characteristics of all DMPA users and study participants Study Participants Characteristic N Age
Years of school Parity No. DMPA injections
All DMPA Users Mean (Range)
DMPA Users Mean (Range)
Other Patients Mean (Range)
379 23.2 (1343)
ii.0 (4136)
z.3 (1532) 12.0 (8-16) 0.9 (o-4] 0
Contraception 1995;51:351-354
Depression and Depot-Medroxyprogesterone
Table 2. Mean CES-D scores among subgroups of DMPA users
have easily arisen by chance. For CES-D scores of 16+ the &i-square with 3 df is 2.72, p = 0.44. For CES-D scores of 22 + the chi-square with 3 df is 1.80, p = 0.62. The proportion of women with depression scores of 16 or greater varied somewhat with years of education (chi-square with 1 df = 2.73, p = 0.10). Parity had no overall relation to the CES-D scores; however, in women whose last pregnancy had ended within 100 days of the first CES-D test, an unexpected, but plausible, effect was observed: Ten women who had a recent live birth had a lower average depression score than eight recently pregnant women who had various adverse pregnancy outcomes (12.0 versus 22.5, p = 0.03). When the last pregnancy had ended more than 100 days before the questionnaire was administered, there was no difference in scores by pregnancy outcome. Individual score differences ranged from 20 points worse to 29 points better, with an average difference of 0.3 points lower (better) on the second test. Questionnaires administered by telephone had slightly lower scores than questionnaires completed in person (13.8 versus 16.3 for the first interview). When CES-D scores were stratified by order of interview (low exposure first versus second) or type of interview (phone versus in-person), no DMPA-related differences emerged.
CES-D Score Characteristic Exposure*
“High” DMPA Exposure’
“LOW” DMPA
80
15.3
16.0
22 28 14 16
15.7 13.4 13.6 19.6
17.2 14.4 14.4 18.4
32 48
17.6 13.3
17.1 15.2
N
l
All subjects Number of injections 1 2 3
4-6 Education 8-11 years 12+ years
*Questionnaire administered one month after a DMPA injection. “Questionnaire administered before the first injection or about following an injection (i.e., immediately preceding a reinjectionj.
90 days
depressive symptoms during exposure to the relatively higher levels of drug a few weeks after each injection (“high” exposure) compared to symptoms either before the first injection or three months after the injection (“low” exposure). The highest depression scores occurred among the women about to have their first injection and those having four or more injections, but these apparent differences could have easily arisen by chance (ANOVA, p = 0.36). The only characteristic that was strongly associated with the scores observed here was years of education (p = 0.02). Table 3 shows the percentage of subjects in each subgroup with scores higher than the threshold values of 16 and 22 points. These percentages are based on each subject’s average score from the two times she completed the CES-D. The percentage of subjects above each threshold based on single, rather than average, test scores was similar (data not shown). The proportion of women with clinically significant depression scores appears greater in subjects with the longest use of DMPA; however, this finding could Table 3. Threshold CES-D scores among DMPA users CES-D score* Characteristic
N
16-37
22-37
AI1 subjects Number of injections 1
80
41%
20%
22 28 14 16
36%
43% 43% 62%
23% 14% 21% 31%
32 48
56% 33%
22% 19%
2 3
4-6 Education 8-11 years 12+ ‘Based
years on each subject’s
average
score across
two tests.
Acetate 353
Discussion Studies of exogenous hormones and mood changes are controversial. Common methodological problems include a poor choice of instrument to assess mood and a failure to consider confounding variables. In this small study a well- validated, simple, widely used instrument, the CES-D, was used to assess depression. The observed scores are higher than those seen in most general population studies,‘f3 but these findings might be expected in a population of young, poor, urban, Hispanic women6r7 Internal validity was demonstrated by the strong effect of low education on scores within the study group. The unexpected finding that the type of outcome of the most recent pregnancy had a strong, but brief, effect on the depression score also supports the validity of using the CES-D to measure depression in this population. If DMPA has a biologic impact on depressive symptoms, one might expect to find more symptoms in women using the drug for a long period of time. The 16 women in this sample who had four or more DMPA injections did have slightly higher average depression scores, and more of these women had scores above clinically relevant thresholds. While this observation is well explained by the play of chance, we had
354
Westhoff et al.
poor statistical power to detect modest effects, and more long-term users need to be studied. Also, in a cross-sectional study like this, we cannot identify women who discontinued use due to depression (and thus never had a chance to participate in the study]. Blood levels of DMPA are somewhat higher during the first month after each injection than two to three months later although data regarding the relative magnitude of the blood levels are limited.4 We found no evidence at all of any association between presumed blood hormone levels and depression scores. The cross-sectional nature of this study and the small number of long-term DMPA users are limitations. The limited effect of DMPA on depression scores combined with powerful effects of other variables is reassuring, but a longitudinal study with more long-term users is needed to evaluate whether depressive symptoms change over time. These data indicate the use of DMPA seems to have little impact on depression in a highly vulnerable population, and that withholding DMPA from such patients because of concerns about depression is not justified. For individual patients who appear depressed, appropriate
Contraception 1995;51:351-354
monitoring cated.
of symptoms
and referral are always indi-
References 1. The Upjohn Company, NDA 20-246. Application summary. Clinical Data Summary. 1992. 2. Frerichs RR, Aneshensel CS, Clark VA. Prevalence of depression in Los Angeles County. Am J Epi 1981 ;113: 691-9. 3. Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psych Measurement 1977;1:385-401. 4. Ortiz A, Hiroi M, Stanczyk FZ, Goebelsmann U, Mishell DR Jr. Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of Depo-MPA. J Clin Endo Metab 1977;44:32-8. 5. Eaton WW, Kessler LG. Rates of symptoms of depression in a national sample. Am J Epi 1981i114528-38. 6. Garrison CZ, Addy CL, Jackson KL, McKeown RE, Wailer JL. The CES-D as a screen for depression and other psychiatric disorders in adolescents. J Am Acad Child Adolesc Psychiatry 1991;30:63wO. 7. Roberts RE. Reliability of the CES-D scale in different ethnic contexts. Psychiatry Res 1980;2:125-34.
Depression in Users of Depo-Medroxyprogesterone
Acetate
Carolyn Westhoff, Daryl Wieland,* and Lorraine Tiezzi Prevalence of depression is high among poor, young, Hispanic inner city women. Depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in this group. DMPA labelling suggests that depression may worsen with use. In order to identify any association of DMPA use with worsening depression, we surveyed an English-speaking subset of DMPA users in a Title-X funded family planning clinic. Eighty women completed the CES-D scale on two occasions: once about four weeks after a DMPA injection when the subject would have been exposed to the highest blood levels, and once immediately prior to an injection when recent blood levels of the drug would be somewhat lower (or absent preceding the first injection). The median CES-D score was 14. The scores were not related to timing of the test (pre- or postinjection). The depression scores were somewhat higher among those women receiving their first DMPA injection during the study period (i.e., unexposed women) and among those women who had received four or more injections. Scores were unrelated to age or parity, but were somewhat higher in women who reported fewer years of education or a recent adverse pregnancy outcome. These data provide little evidence of increasing depression with long-term use of DMPA and no evidence of a short-term effect of dose (within the contraceptive range) on mood. Women at risk of depression should not be denied DMPA as a contraceptive choice. CONTRACEPTION 1995;51:351354 KEY WORDS: depression, contraception,
progesterone
Introduction epot-medroxyprogesterone acetate (DMPA) was approved by the FDA for contraceptive use in November 1992. In the precaution section, the package labelling states that “patients who
D
Columbia University School of Public Health and College of Physicians and Surgeons, New York, NY and ‘Department of Obstetrics and Gynecology, Mt. Sinai Medical Center, New York, NY Name and address for correspondence: C. Westhoff, MD, Department of Obstetrics and Gynecology, Columbia University, 630 West 168 St., New York, N.Y. 10032. Tel: (212) 305-7070; Fax (212) 305-3869 Submitted for publication November 15, 1994 Revised April 11, 1995 Accepted for publication April 11, 1995
0 1995 Elsevier Science Inc. 655 Avenue of the Americas, New York,
NY 10010
have a history of psychic depression should be carefully observed and the drug not be readministered if the depression recurs.” This precaution was based on clinical data submitted to the FDA showing that 1.5% of 4200 users reported depression and 0.5% discontinued use of DMPA for this reason.’ The individuals who use the Columbia-Presbyterian Medical Center Family Planning Clinics are predominantly young, poor, urban, Hispanic females; these characteristics are associated with a high prevalence of depression.2 Substantiating this, in the last six months of 1994, 87 patients attending these clinics were referred to psychiatry for evaluation and treatment of depression. Since its approval by the FDA, DMPA has become a popular contraceptive choice in this population. The purpose of this study was to identify whether some aspects of DMPA use are associated with depressive symptoms in this high risk population.
Methods The study sample was selected from all patients at the Columbia-Presbyterian Medical Center Family Planning Clinics who were DMPA users during December 1993 and January 1994. All of their medical records were abstracted for routinely collected data including age, race, preferred language, years of education, pregnancy history, and the dates of all DMPA injections. English-speaking or bilingual subjects who sought a first or subsequent DMPA injection in the clinic during these months were invited into this IF&approved study by a single clinician (DW). If a DMPA user was seen by another clinician, she was not invited to participate in the study. Participation consisted of completing a brief set of questions about mood during the previous week on two occasions about two months apart. The questions were completed either in person or over the telephone. In addition, a group of Englishspeaking patients who were not using DMPA were asked to complete the interview once. The Community Epidemiology Survey-Depression Scale (CES-D) was used to assess depressive symptoms.3 This short self-report scale is designed to ISSN OOlO-7824/95/$9.50 SSDI OOl O-7824(95)00100-O
352
Contraception 1995;51:351-354
Westhoff et al.
measure depressive symptoms during the previous week in the general population; this scale has been extensively validated and widely used in population studies of depressive symptoms. The possible scores range from 0 to 60, and a score of 16 or greater is frequently used as a threshold suggesting risk of clinical depression; however, this threshold has poor specificity and is not appropriate in all populations.2 For adolescent females, a score of 22 or greater may be a more appropriate threshold. The timing of the two questionnaires for each DMPA user was intended to correspond to intervals of relatively high and low exposure.4 The high exposure week was one month after an injection of DMPA. The low exposure week was immediately before the first injection or before a scheduled reinjection. Because subjects might report fewer symptoms and thus have a systematically lower score on the second test,5 the order of the tests was alternated so that some subjects were first tested after the high exposure week and others were first tested after the low exposure week. Baseline characteristics of the study subjects were compared to the baseline characteristics of all DMPA users. The main outcome of interest was whether the CES-D scores were related to the level of DMPA exposure (“high” versus “low”) or to the duration of use of DMPA as measured by the total number of injections received. The association between CES-D scores and baseline characteristics was assessed in order to identify whether expected associations were seen in the study population. These variables as well as test order and test method (in person versus by telephone) were assessed to identify and adjust for any confounding effect on the main associations. The CES-D scores were right skewed; however, transformations performed to normalize the distribution had no important effect on any of the associations considered. The scores that are presented are untransformed. T-tests, paired and unpaired, and analysis of variance were used to compare mean CES-D scores between subjects. The proportion of scores falling above the thresholds of 16 and 22 points in subgroups of sub-
jects were compared using a &i-square tinuity correction.
test with con-
Results Three-hundred-seventy-nine DMPA users were identified by record review during December 1993 and January 1994. Eighty-two DMPA users were invited to participate in the studyj two were lost to follow-up after the first test. Twenty-six consecutive Englishspeaking non-DMPA users were also interviewed during a single clinic visit. No women refused to participate. Age and parity were similar between the 80 study subjects who completed two CES-D tests and all 379 DMPA users (Table 1). The study subjects reported slightly more years of school (p = 0.04). This is likely to have occurred because speaking and reading English was a requirement for participation in the study. Only 39 subjects considered English to be their first language, but CES-D scores were not related to whether the first language was English or Spanish. Seventy-one of the subjects were Hispanic, and most of these were Dominican; the remaining nine subjects were black. The CES-D scores in this sample were unrelated to ethnicity. The overall mean CES-D score in the DMPA users was 15.6 with a range from 0 to 37 points. The characteristics of the 26 English-speaking DMPA non-users who were interviewed are also shown in Table 1. Their mean CES-D score was 14.4 with a range from 0 to 38 points. Overall, this small group of non-users attending the same clinic was similar to the DMPA users for these characteristics. In the full group of DMPA users there were 73 women whose last injection had been given more than 100 days before the medical record was abstracted. These women were presumed to be discontinuing the method; their age, parity, and education was similar to the continuing users, but they had fewer injections than the continuing users which includes the study subjects. Table 2 shows that there was no evidence of more
Table 1. Baseline characteristics of all DMPA users and study participants Study Participants Characteristic N Age
Years of school Parity No. DMPA injections
All DMPA Users Mean (Range)
DMPA Users Mean (Range)
Other Patients Mean (Range)
379 23.2 (1343)
ii.0 (4136)
z.3 (1532) 12.0 (8-16) 0.9 (o-4] 0
Contraception 1995;51:351-354
Depression and Depot-Medroxyprogesterone
Table 2. Mean CES-D scores among subgroups of DMPA users
have easily arisen by chance. For CES-D scores of 16+ the &i-square with 3 df is 2.72, p = 0.44. For CES-D scores of 22 + the chi-square with 3 df is 1.80, p = 0.62. The proportion of women with depression scores of 16 or greater varied somewhat with years of education (chi-square with 1 df = 2.73, p = 0.10). Parity had no overall relation to the CES-D scores; however, in women whose last pregnancy had ended within 100 days of the first CES-D test, an unexpected, but plausible, effect was observed: Ten women who had a recent live birth had a lower average depression score than eight recently pregnant women who had various adverse pregnancy outcomes (12.0 versus 22.5, p = 0.03). When the last pregnancy had ended more than 100 days before the questionnaire was administered, there was no difference in scores by pregnancy outcome. Individual score differences ranged from 20 points worse to 29 points better, with an average difference of 0.3 points lower (better) on the second test. Questionnaires administered by telephone had slightly lower scores than questionnaires completed in person (13.8 versus 16.3 for the first interview). When CES-D scores were stratified by order of interview (low exposure first versus second) or type of interview (phone versus in-person), no DMPA-related differences emerged.
CES-D Score Characteristic Exposure*
“High” DMPA Exposure’
“LOW” DMPA
80
15.3
16.0
22 28 14 16
15.7 13.4 13.6 19.6
17.2 14.4 14.4 18.4
32 48
17.6 13.3
17.1 15.2
N
l
All subjects Number of injections 1 2 3
4-6 Education 8-11 years 12+ years
*Questionnaire administered one month after a DMPA injection. “Questionnaire administered before the first injection or about following an injection (i.e., immediately preceding a reinjectionj.
90 days
depressive symptoms during exposure to the relatively higher levels of drug a few weeks after each injection (“high” exposure) compared to symptoms either before the first injection or three months after the injection (“low” exposure). The highest depression scores occurred among the women about to have their first injection and those having four or more injections, but these apparent differences could have easily arisen by chance (ANOVA, p = 0.36). The only characteristic that was strongly associated with the scores observed here was years of education (p = 0.02). Table 3 shows the percentage of subjects in each subgroup with scores higher than the threshold values of 16 and 22 points. These percentages are based on each subject’s average score from the two times she completed the CES-D. The percentage of subjects above each threshold based on single, rather than average, test scores was similar (data not shown). The proportion of women with clinically significant depression scores appears greater in subjects with the longest use of DMPA; however, this finding could Table 3. Threshold CES-D scores among DMPA users CES-D score* Characteristic
N
16-37
22-37
AI1 subjects Number of injections 1
80
41%
20%
22 28 14 16
36%
43% 43% 62%
23% 14% 21% 31%
32 48
56% 33%
22% 19%
2 3
4-6 Education 8-11 years 12+ ‘Based
years on each subject’s
average
score across
two tests.
Acetate 353
Discussion Studies of exogenous hormones and mood changes are controversial. Common methodological problems include a poor choice of instrument to assess mood and a failure to consider confounding variables. In this small study a well- validated, simple, widely used instrument, the CES-D, was used to assess depression. The observed scores are higher than those seen in most general population studies,‘f3 but these findings might be expected in a population of young, poor, urban, Hispanic women6r7 Internal validity was demonstrated by the strong effect of low education on scores within the study group. The unexpected finding that the type of outcome of the most recent pregnancy had a strong, but brief, effect on the depression score also supports the validity of using the CES-D to measure depression in this population. If DMPA has a biologic impact on depressive symptoms, one might expect to find more symptoms in women using the drug for a long period of time. The 16 women in this sample who had four or more DMPA injections did have slightly higher average depression scores, and more of these women had scores above clinically relevant thresholds. While this observation is well explained by the play of chance, we had
354
Westhoff et al.
poor statistical power to detect modest effects, and more long-term users need to be studied. Also, in a cross-sectional study like this, we cannot identify women who discontinued use due to depression (and thus never had a chance to participate in the study]. Blood levels of DMPA are somewhat higher during the first month after each injection than two to three months later although data regarding the relative magnitude of the blood levels are limited.4 We found no evidence at all of any association between presumed blood hormone levels and depression scores. The cross-sectional nature of this study and the small number of long-term DMPA users are limitations. The limited effect of DMPA on depression scores combined with powerful effects of other variables is reassuring, but a longitudinal study with more long-term users is needed to evaluate whether depressive symptoms change over time. These data indicate the use of DMPA seems to have little impact on depression in a highly vulnerable population, and that withholding DMPA from such patients because of concerns about depression is not justified. For individual patients who appear depressed, appropriate
Contraception 1995;51:351-354
monitoring cated.
of symptoms
and referral are always indi-
References 1. The Upjohn Company, NDA 20-246. Application summary. Clinical Data Summary. 1992. 2. Frerichs RR, Aneshensel CS, Clark VA. Prevalence of depression in Los Angeles County. Am J Epi 1981 ;113: 691-9. 3. Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psych Measurement 1977;1:385-401. 4. Ortiz A, Hiroi M, Stanczyk FZ, Goebelsmann U, Mishell DR Jr. Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of Depo-MPA. J Clin Endo Metab 1977;44:32-8. 5. Eaton WW, Kessler LG. Rates of symptoms of depression in a national sample. Am J Epi 1981i114528-38. 6. Garrison CZ, Addy CL, Jackson KL, McKeown RE, Wailer JL. The CES-D as a screen for depression and other psychiatric disorders in adolescents. J Am Acad Child Adolesc Psychiatry 1991;30:63wO. 7. Roberts RE. Reliability of the CES-D scale in different ethnic contexts. Psychiatry Res 1980;2:125-34.