Elsevier

Psychoneuroendocrinology

Volume 32, Issue 7, August 2007, Pages 843-853
Psychoneuroendocrinology

Influences of hormone-based contraception on depressive symptoms in premenopausal women with major depression

https://doi.org/10.1016/j.psyneuen.2007.05.013Get rights and content

Summary

Objective

Hormone-based contraceptives affect mood in healthy women or in women with premenstrual dysphoric disorder (PMDD). No study has yet examined their association with mood in women with major depressive disorder (MDD). The purpose of this study was to determine whether estrogen–progestin combination or progestin-only contraceptives are associated with depression severity, function and quality of life, or general medical or psychiatric comorbidity in women with MDD.

Methods

This analysis focused on a large population of female outpatients less than 40 years of age with non-psychotic MDD who were treated in 18 primary and 23 psychiatric care settings across the US, using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Baseline demographic and clinical information was gathered and compared between three groups based on hormonal use: combination (estrogen–progestin)(N=232), progestin-only (N=58), and no hormone treatment (N=948).

Results

Caucasians were significantly more likely to use combined hormone contraception. Women on progestin-only had significantly more general medical comorbidities; greater hypersomnia, weight gain and gastrointestinal symptoms; and worse physical functioning than women in either of the other groups. Those on combined hormone contraception were significantly less depressed than those with no hormone treatment by the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated. The combined hormone group also demonstrated better physical functioning and less obsessive-compulsive disorder (COCD) comorbidity than either of the other groups.

Conclusions

Synthetic estrogen and progestins may influence depressive and physical symptoms in depressed women.

Introduction

The use of hormonal forms of contraception is common among women of reproductive age, the most common being a combination of synthetic estrogen (ethinyl estradiol) and synthetic progesterone (progestin). Studies that have examined the effects of these hormone treatments on mood have predominantly been conducted in populations of women with Premenstrual Dysphoric Disorder (PMDD) or healthy women. Early studies using oral contraceptives with high progestin doses reported depression as a possible side effect in normal women in case series and small case-control studies (Nilson and Almgren, 1968; Herzberg et al., 1970; Worsley and Change, 1978). A large epidemiological-based study found that among women with PMDD who were starting hormone-based contraceptives, most women showed no change in mood, with mood improving in some women and worsening in others (Joffe et al., 2003). This finding in a community-based study agrees with that of an earlier report that hormone-based contraceptives have no effect on mood in this population (Oinonen and Mazmanian, 2002). Studies of “normal women” given hormone-based contraceptives generally report little change in mood (Masse et al., 1998), or they report an altered pattern of mood changes across the menstrual cycle when women on hormone-based contraceptives were compared to those on non-hormone contraceptives (Abraham et al., 2003). A recent placebo controlled study of adolescents given oral contraceptives showed “improvement” in CES-D scores in both placebo treated and oral contraceptive treated adolescents (O’Connell et al., 2007).

In addition to hormone-based contraceptives that include both an estrogen and progestin component, alternative progestin-only forms of contraception are now in use (e.g., Depo-Provera and the Norplant surgical implant), and studies have examined their relationship to mood. In general, progestin-only forms of contraception are longer acting and thus require less compliance burden than daily oral contraceptive administration. In a large multi-site study, Westhoff et al. (1998a) reported that among women who chose Norplant (n=910), those who dropped out of the study (n=93) had higher depression scores than those who continued with Norplant. Among those who stayed in the study, depression scores were unchanged after 6 months. A similar pattern was observed in women who elected to use Depo-Provera (n=495) (Westhoff et al., 1998b); the women who dropped out (n=218) had higher depression scores than those who remained on Depo-Provera. The depression scores of women who remained on Depo-Provera showed minimal change over 1 year. A randomized placebo-controlled trial of the progestin-only contraceptive norethisterone enanthate in 180 postpartum women found significant increases in the Montgomery Asberg and Edinburgh Postnatal Depression Scales (Lawrie et al., 1998). Thus, there is some literature suggesting that progestin-only forms of contraceptive may worsen mood in women who are susceptible to depression.

Despite these findings of the effects of hormone-based contraceptives on mood, no studies have examined the effects of these hormonal treatments on the symptoms of major depression. Studies in non-human primates have found that the main estrogen in humans, estradiol, modulates brain serotonin systems at multiple sites including synthesis, reuptake and receptors (Shively and Bethea, 2004). Therefore, synthetic estrogen plus progestin (combined) contraceptives that lead to changes in estrogens could influence brain serotonin systems. Some studies have examined the effects of estradiol on depressed mood in women with altered reproductive hormones such as post-partum depression or depression during the perimenopause and found mood improvements in randomized controlled trials (Gregoire et al., 1996; Schmidt et al., 2000; Soares et al., 2001). However, no beneficial effects of estradiol alone were observed in post-menopausal women with depression (Morrison et al., 2004). These studies utilized estradiol rather than ethinyl estradiol so it is unclear whether similar effects would be observed with combined hormone-based contraceptives in normally cycling premenopausal women.

Despite suggestions that hormone-based contraceptives might affect mood, the use of these forms of contraception remain prevalent in reproductive aged women, those who are at the greatest risk for development of depression. The purpose of this study was to examine the association of hormone-based contraceptives with mood in a population of premenopausal women with non-psychotic major depressive disorder (MDD) to determine whether those that use combined hormone contraception, progestin-only contraception, or neither differ in terms of depression severity, function and quality of life, and general medical and psychiatric comorbidity.

Section snippets

Overview

This report evaluates a broadly representative clinical sample of outpatients with nonpsychotic MDD enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (www.star-d.org). The rationale and design of STAR*D have been detailed elsewhere (Fava et al., 2003; Rush et al., 2004).

Briefly, the aim of STAR*D was to define prospectively which of several treatments are most effective for outpatients with non-psychotic MDD who had an unsatisfactory clinical outcome to an

Results

Table 1 shows the demographic data and the results of comparisons made between the three groups: premenopausal women on combination estrogen- and progestin-based contraceptives (n=232), those on progestin-only-based contraceptives (n=58) and those on no hormonal contraceptives (n=948). The combination hormone group had a significantly larger proportion of Caucasians than either of the other two groups. The combination group also was younger with more years of education. Subsequent analyses were

Discussion

Hormone-based contraceptives are commonly used by women of reproductive age, the age in which recurrent depressive episodes are commonly seen. The large number of participants enrolled into STAR*D enabled us to examine whether there are any systematic differences among premenopausal depressed women using combination hormone-based contraceptives, those using progestin-only-based contraceptives (primarily depot Provera or Norplant) and those not taking exogenous reproductive hormones. The data

Role of funding source

Funding for this study was provided by NIMH contract N01MH90003 to UT Southwestern Medical Center at Dallas (P.I.: A.J. Rush). As a contract, NIMH had a role in the study design. It had no further role in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the paper for publication.

Conflict of interest

E.A. Young has no financial disclosures. S.R. Wisniewski has no financial disclosures. J. Barkin has no financial disclosures.

Acknowledgements

This project has been funded with Federal funds from the National Institute of Mental Health, National Institutes of Health, under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (P.I.: A.J. Rush).

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

We appreciate the support of Bristol-Myers

References (41)

  • P.J. Schmidt et al.

    Estrogen replacement in perimenopause-related depression: a preliminary report

    Am. J. Obstet. Gynecol.

    (2000)
  • C. Westhoff et al.

    Depressive symptoms and Norplant contraceptive implants

    Contraception

    (1998)
  • C. Westhoff et al.

    Depressive symptoms and depo-provera

    Contraception

    (1998)
  • A. Worsley et al.

    Oral contraceptive and emotional states

    J. Psychosom. Res.

    (1978)
  • S. Abraham et al.

    Oral contraception and cyclic changes in premenstrual and menstrual experiences

    J. Psychosom. Obstet. Gynaecol.

    (2003)
  • Diagnostic and Statistical Manual of Mental Disorders

    (1994)
  • Endicott, J., Nee, J., Harrison, W., Blumenthal, R., 1993. Quality of life enjoyment and satisfaction questionnaire: a...
  • M. Fava et al.

    Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D

    Psychol. Med.

    (2004)
  • M. Hamilton

    A rating scale for depression

    J. Neurol. Neurosurg. Psychiat.

    (1960)
  • M. Hamilton

    Development of a rating scale for primary depressive illness

    Br. J. Soc. Clin. Psychol.

    (1967)
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