Association of Hormonal Contraceptive Use With Reduced Levels of Depressive Symptoms

A National Study of Sexually Active Women in the United States

Katherine M. Keyes; Keely Cheslack-Postava; Carolyn Westhoff; Christine M. Heim; Michelle Haloossim; Kate Walsh; Karestan Koenen

Disclosures

Am J Epidemiol. 2013;178(9):1378-1388.

Materials and Methods

Sample

Data were drawn from the National Longitudinal Study of Adolescent Health,^[23] an ongoing nationally representative study designed to address health, behaviors, and relationships. The study began with approximately 90,000 adolescents aged 12–21 years who were sampled at school in 1994–1995; approximately 20,000 of these adolescents underwent in-depth home interviews and longitudinal follow-up. Follow-up interviews were conducted in 1996 (wave 2), 2001–2002 (wave 3), and 2007–2008 (wave 4).

The present study focused on the subset of participants who completed a wave 4 interview in 2007–2008, at ages 25–34 years. Figure 1 outlines the exclusion criteria for the present sample. Women who were not sexually active in the past year were not asked about contraceptive use; thus, we did not include them in the analytical sample. The sample size for analysis was 6,654.

(Enlarge Image)

Figure 1.

Selection of the study sample from participants in the wave 4 interview (ages 25–34 years) of the National Longitudinal Study of Adolescent Health (Add Health), 2007–2008.

Measures

Contraceptive Use in Wave 4 Women who had had a sex partner in the past year were asked whether they used any form of birth control or disease prevention. We divided the sample into groups based on World Health Organization categories of contraception effectiveness.^[24]

The first group included women using methods that are rated as highly effective, and included vasectomy, intrauterine devices (IUDs), and tubal ligation (n = 831; 12.5%). We did not have information on use of hormonal IUDs versus nonhormonal IUDs; however, hormonal IUDs would probably comprise a small proportion of total IUD use in this sample, which was already low (4.5%). A second category included methods rated as effective; these included combination hormonal contraceptives in the form of the contraceptive pill, patch, or ring (n = 2,393; 36.0%). We analyzed women using known progestin-only forms of contraception (i.e., Depo-Provera (Pfizer Inc., New York, New York) or Norplant (Wyeth Pharmaceuticals, Radnor, Pennsylvania)) separately (n = 298; 4.5%) and report results separately from those for the pill, patch, and ring group. Among women who did not use a highly effective or effective method, a third category included women who used condoms, a diaphragm, a vaginal sponge, or the withdrawal method (n = 1,913; 28.8%). Among women who did not use any of the above methods, a fourth category included the least effective contraceptive methods: periodic abstinence, spermicides, and contraceptive film (n = 91; 1.4%). Finally, 17.0% (n = 1,128) of women in the sample did not report any contraceptive use with a current partner. Because of low prevalence, women using the least effective contraceptive methods were combined with women using no contraception.

Contraceptive Uuse in Waves 1–3 In waves 1 and 2, women were asked whether they were currently taking birth control pills (wave 1: 8.2%; wave 2: 8.6%). We note that the wave 1 and 2 interviews were conducted between 1994 and 1996, before the contraceptive patch and ring formulations were introduced. We did not have information on known progestin-only forms of contraception in waves 1 and 2. However, fewer than 2% of women have ever used these forms of contraception;^[25] thus, while there may have been some women in the referent group who were using a hormonal form of contraception, the number is unlikely to have been appreciable.

In wave 3, questions on contraceptive use mirrored the wave 4 measures. We included anyone using a pill, patch, or ring and users of known progestin-only products as hormonal contraceptive users (50.4%). We created dichotomous indicators for these hormonal contraceptive users versus all other women. As noted above, information on hormonal IUDs was not included, but the number of women using these devices was probably negligible.

Depressive Symptoms and Suicide Attempts in Waves 1–4 The presence of depressive symptoms during the past 7 days was assessed in all waves using the Center for Epidemiologic Studies Depression Scale (CES-D).^[26,27] In waves 1 and 2, the 20-item CES-D Scale was used, with each item scored 0–3, for a maximum score of 60. In waves 3 and 4, the 10-item CES-D Scale was used, with each item scored 0–3, for a maximum score of 30. Both the 10-item and the 20-item CES-D have well-documented reliability and validity.^[26–28] In waves 3 and 4, a CES-D score greater than or equal to 11 was considered a high level of depressive symptoms.^[29] In each wave, respondents were also asked how many times they had attempted suicide in the past year (dichotomized at 1 or more attempts).

Other Covariates We assessed a range of covariates for capturing information on the health and lifestyles of sexually active women. All covariates included are shown in Table 1 . Demographic factors included age, race/ethnicity, education, and parity. Relationship factors included past-year monogamy and total lifetime number of vaginal sex partners. Health-related factors included current body mass index (weight (kg)/height (m)²), derived using weight and height measured by the interviewer at the time of the interview or imputed with self-report data when measured data were unavailable; participation in any individual sports during the past week (e.g., running or jogging); visiting a dentist during the last 2 years; undergoing a routine checkup by a physician during the last 2 years; and current smoking status. We also included the centrality of religion to the respondent, given that religion may be important in the decision to use contraceptives^[30,31] and is also associated with depression.^[32]

Statistical Analysis

First, we examined whether women using various forms of contraception or no contraception (4-level categorical variable) varied with regard to health-related covariates. We used chi-square tests for categorical outcomes and t tests for continuous outcomes. We created a propensity score using the binary variable of hormonal contraceptive use versus none as the outcome. Covariates used to create the propensity score included health-related covariates as well as design variables (study stratum (geographic area), primary sampling unit, and sample weight), as is recommended for propensity score analysis in complex surveys.^[33] We examined the distribution of contraception categories within quintiles of the propensity score for sufficient sample sizes to conduct the analysis and controlled for propensity score in additional regression models.^[34] Second, we tested whether women differed with regard to wave 4 depression symptoms, a high level of depressive symptoms, and past-year suicide attempts based on wave 4 contraceptive use. Women using the least effective contraceptives or no contraceptives were designated the referent group. Linear regression was used for depressive symptoms and logistic regression for high levels of depressive symptoms and past-year suicide attempts. Results of regression analyses were first unadjusted and then adjusted for all of the health-related variables listed in Table 1; analyses were also carried out with adjustment for propensity score. In addition, analyses of depression outcomes were also controlled for prior-wave highest depression score, and analyses of suicide attempts were also controlled for any prior suicide attempt. Users of known progestin-only products were analyzed separately. Third, longitudinal associations were assessed examining wave 3 hormonal contraceptive use (versus all other wave 3 respondents), wave 4 hormonal contraceptive use (versus all other wave 4 respondents), and high levels of depressive symptoms and past-year suicide attempts in both wave 3 and wave 4—all with logistic regression models. Analyses were conducted using SAS-callable (SAS Institute Inc., Cary, North Carolina) SUDAAN (RTI International, Research Triangle Park, North Carolina) and incorporated design weights.

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Table 1. Distributions of Sociodemographic Characteristics, Relationship Factors, and Health Behaviors Among Sexually Active Nonpregnant Women Aged 25–34 Years in a Nationally Representative US Sample, National Longitudinal Study of Adolescent Health, 2007–2008
Characteristic	Effectiveness of Contraceptive Method								Significance Test^b	Degrees of Freedom	P Value
	Highly Effective (n = 831)		Effective (Hormonal)^a (n = 2,393)		Less Effective (n = 1,913)		Least Effective or None Used (n = 1,219)
	%	Mean	%	Mean	%	Mean	%	Mean
Sociodemographic factors
Age, years		28.8		28.2		28.5		28.7	11.4	3	<0.01
Parity (any children)	91.7		38.5		55.8		61.6		76.8	3	<0.01
Highest level of education completed
Less than high school	9.5		3.0		6.9		13.3		32.4	6	<0.01
High school	72.5		44.1		62.6		68.4
College or more	17.9		52.9		30.5		18.3
Race/ethnicity
Non-Hispanic	75.8		75.2		58.4		69.5		6.1	9	<0.01
White
American Indian, Alaska Native, Asian, or Pacific Islander	3.2		3.5		5.1		3.3
Black	11.7		10.3		23.7		13.0
Hispanic	9.3		10.9		12.8		14.2
Relationship factors
In a monogamous sexual partnership	81.8		76.2		66.0		80.0		10.6	3	<0.01
Lifetime no. of vaginal sex partners		9.6		9.0		9.6		10.5	1.1	3	0.36
Health behaviors and other indicators of interest
Body mass index^c		29.0		26.9		29.5		31.4	27.0	3	<0.01
Any individual sports (e.g., running) in the past week	18.2		29.3		17.9		18,3		12.8	3	<0.01
Undergoing a routine checkup by a physician in the past 2 years	82.7		87.8		81.0		76.0		10.7	3	<0.01
Visiting a dentist in the last 2 years	58.0		67.4		55.4		50.6		14.0	3	<0.01
Smoking status
Regular smoker (≥1 cigarette on ≥25 days in past month)	34.2		16.0		26.1		32.9		9.8	6	<0.01
Occasional smoker (≥1 cigarette on ≥1 day but <25 days in past month)	7.7		13.9		12.8		12.0
Nonsmoker (no cigarettes in past month)	58.1		70.1		61.1		55.2
Importance of religion
Not important	12.6		15.5		11.1		10.1		1.6	9	0.12
Somewhat important	32.9		33.9		30.2		32.9
Extremely important	41.5		39.6		46.2		45.2
More important than anything else	12.9		10.9		12.4		11.8
History of depression, suicide attempts, and hormonal birth control use
Mean depression score^d
Wave 1		10.4		8.5		10.0		10.8	12.2	3	<0.01
Wave 2		9.2		3.7		7.0		13.0	10.6	3	<0.01
Wave 3		5.2		4.6		5.2		5.7	6.9	3	<0.01
Any past-year suicide attempt
Wave 1	7.7		5.5		6.0		8.3		1.3	3	0.27
Wave 2	9.0		3.7		6.7		5.8		5.3	3	<0.01
Wave 3	1.8		2.6		2.3		4.5		1.3	3	0.29
Reported hormonal birth control use at a past interview^e	53.0		68.5		48.5		51.1		19.2	3	<0.01

Abbreviation: CES-D, Center for Epidemiologic Studies Depression Scale.
^a "Hormonal birth control" included contraceptive pills, patches, and ring formulations. Users of Depo-Provera (Pfizer Inc., New York, New York) and Norplant (Wyeth Pharmaceuticals, Radnor, Pennsylvania) were analyzed separately; demographic information for this group is available upon request.
^b Chi-square test for categorical covariates; t test for continuous covariates.
^c Weight (kg)/height (m)².
^d Depression score in waves 1 and 2 was measured with the 20-item CES-D (possible range of scores, 0–60). Depression score in wave 3 was measured with the 10-item CES-D (possible range of scores, 0–30).
^e Hormonal birth control assessed in waves 1 and 2 included oral contraceptives only. Hormonal birth control assessed in wave 3 included pills, patches, rings, Depo-Provera, and Norplant.

Table 2. Distribution ofWomen Aged 25–34 Years Into Contraception Categories (%) by Quintile of Propensity Score,a National Longitudinal Study of Adolescent Health, 2007–2008
	Effectiveness of Contraceptive Method
Quintile of Propensity Score	Highly Effective (n = 831)	Effective (Hormonal) (n = 2,393)	Less Effective (n = 1,913)	Least Effective or None Used (n = 1,310)
5 (>0.83)	4.2	74.5	15.1	6.2
4 (0.72–0.83)	8.0	49.0	27.5	15.5
3 (0.58–0.71)	12.4	35.9	32.6	19.2
2 (0.39–0.57)	17.4	22.7	33.2	26.8
1 (<0.39)	18.0	10.4	41.0	30.6

^a Propensity to use hormonal contraceptives. Covariates included in the propensity score included study stratum (geographic area), primary sampling unit, sample weight, age, education, race/ethnicity, smoking, parity, monogamy (dichotomous indicator) and number of sex partners in the past year (continuous measure), importance of religion, regular engagement in an individual sport (e.g., running or jogging), body mass index, visiting the dentist in the last 2 years, undergoing a routine checkup by a physician in the last 2 years, prior use of hormonal birth control, prior depressive symptoms, and prior suicide attempts.

Table 3. Association Between Hormonal Contraceptive Use and Depressive Symptoms in a Nationally Representative US Sample of Sexually Active NonpregnantWomen Aged 25–34 Years, National Longitudinal Study of Adolescent Health, 2007–2008
Measure of Depressive Symptoms and Effectiveness of Contraceptive Method	No. of Women	Mean Value	β	OR	95% CI	Adjusted β^a	Adjusted OR^a	95% CI	Propensity Score^b	95% CI
Past-week CES-D depression score (continuous)
Highly effective^c	831	6.65	−0.67		−1.53, 0.19	−0.38		−1.06, 0.30	−0.89	−1.68, 0.04
Effective (hormonal)^d	2,393	5.61	−1.71*		−2.37, −1.05	−0.71*		−1.30, −0.11	−1.04*	−1.73, −0.35
Less effective^e	1,913	6.90	−0.42		−1.12, 0.27	−0.24		−0.86, 0.39	−0.39	−1.08, 0.29
Least effective or none used^f	1,310	7.32	0		Referent	0		Referent	0	Referent
High past-week depression score (CES-D score ≥11)
Highly effective	831	20.10		0.80	0.53, 1.20		0.91	0.61, 1.35	0.74	0.50, 1.09
Effective (hormonal)	2,393	14.35		0.53*	0.39, 0.72		0.81	0.58, 1.14	0.68*	0.49, 0.94
Less effective	1,913	21.88		0.89	0.65, 1.22		0.99	0.70, 1.41	0.89	0.65, 1.22
Least effective or none used	1,310	23.94		1	Referent		1	Referent	1	Referent
Any suicide attempt in the past year
Highly effective	831	3.59		1.71	0.65, 4.50		1.30	0.45, 3.91	1.32	0.48, 3.58
Effective (hormonal)	2,393	0.67		0.31*	0.12, 0.82		0.38*	0.15, 0.97	0.37*	0.14, 0.95
Less effective	1,913	2.49		1.17	0.53, 2.59		1.18	0.55, 2.55	1.20	0.54, 2.68
Least effective or none used	1,310	3.11		1	Referent		1	Referent	1	Referent

Abbreviations: CES-D, Center for Epidemiologic Studies Depression Scale; CI, confidence interval; OR, odds ratio. * P < 0.05.
^a Results were adjusted for age, education, race/ethnicity, smoking, parity, past-year monogamy, lifetime number of vaginal sex partners, importance of religion, regular engagement in an individual sport (e.g., running or jogging), body mass index, visiting the dentist in the last 2 years, going to a physician for a routine checkup in the last 2 years, and prior use of hormonal birth control. Analyses of depression outcomes were also controlled for prior wave highest depression score; analyses of suicide attempts were also controlled for any prior suicide attempt.
^b Propensity to use hormonal contraceptives.
^c Included vasectomy, intrauterine devices, and tubal ligation.
^d Included combination hormonal contraceptives in the form of the contraceptive pill, patch, or ring. Women using known progestin-only forms of contraception (i.e., Depo-Provera (Pfizer Inc., New York, New York) or Norplant (Wyeth Pharmaceuticals, Radnor, Pennsylvania)) were analyzed separately.
^e Included condoms, diaphragms, vaginal sponges, and the withdrawal method.
^f Included periodic abstinence, spermicides, and contraceptive film.