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.

Abstract and Introduction

Abstract

An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994–2008), focusing on women aged 25–34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25–34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = −1.04, 95% confidence interval: −1.73, −0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.

Introduction

An estimated 80% of sexually active women in the United States use hormonal contraception, most typically oral contraceptives, to prevent pregnancy.^[1] In addition to providing effective pregnancy prevention, hormonal contraception offers many health benefits,^[2–4] though its use remains a risk factor for venous thromboembolism and other vascular disease outcomes.^[5]

Little research has focused on the association of hormonal contraceptive use with mental health outcomes, such as depressive symptoms, and more severe manifestations of mood disturbance, such as suicide attempts. Approximately 17% of women experience major depression during their lifetime, with incidence being highest during the reproductive years,^[6] and many more experience depressive symptoms that do not necessarily cross the threshold to a diagnosis but may be disabling.^[7,8] While a role for hormones such as estrogen and progesterone in the etiology of depressive symptoms has been hypothesized,^[9–11] the association remains inadequately understood. Clinical studies have indicated that precipitous changes in estrogen levels may trigger depressive episodes among women at risk for depression, particularly during the late luteal phase of the menstrual cycle and during postpartum and perimenopausal periods,^[12,13] and that women with major depression generally have lower estradiol levels than controls.^[14,15] Given that hormonal contraception methods introduce synthetic estrogen and progestin and modulate the physiological cycle, an examination of the role of hormonal contraception in mood problems is warranted.

Few population-based studies have evaluated the association between hormonal contraceptive use and depressive symptoms. Among 3 population-based studies conducted within the last 15 years, 2 found no consistent evidence of an association (positive or negative) between hormonal contraceptive use and depressive symptoms,^[16,17] while a recent population-based study in Finland found that hormonal contraceptive use reduced levels of depressive symptoms.^[18] A recent study of long-term mortality based on oral contraceptive use found an increase in violent deaths, including suicide, among oral contraceptive users compared with nonusers,^[19] although 2 other large studies found no increase in suicide risk for oral contraceptive use.^[20,21] To our knowledge, no studies have examined oral contraceptive use in relation to suicide attempts, which are more common and have different risk factors than completed suicide.^[22] Thus, there remains limited evidence regarding potential associations between hormonal contraceptive use and depressive symptoms or suicidality, despite widespread use of these methods for pregnancy prevention and other outcomes.

In the present study, we utilized data from a nationally representative US longitudinal study to investigate the association between contraceptive use and depressive symptoms, as well as suicide attempts. First, we compared women who were using various forms of hormonal and nonhormonal contraception with women who were using no contraception with regard to various dimensions of health, including exercise, body mass index, smoking, and engagement with health professionals. Second, we tested the association between contraceptive use and concurrent depressive symptoms, as well as past-year suicide attempts, while controlling for health-related dimensions that varied across contraceptive users. We used traditional adjustment as well as propensity score adjustment to control for sources of confounding. Lastly, we examined longitudinally whether hormonal contraceptive use predicted depressive symptoms/suicide attempts and whether depressive symptoms/suicide attempts predicted hormonal contraceptive use.

1 2 3 4

Next Section

Abstract and Introduction
Materials and Methods
Results
Discussion
References

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.