The use of hormonal contraceptive agents and mood disorders in women

doi:10.1016/j.jad.2012.03.030

Journal of Affective Disorders

Volume 140, Issue 1, September 2012, Pages 92-96

https://doi.org/10.1016/j.jad.2012.03.030 Get rights and content

Abstract

Background

Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based sample of women.

Methods

This study examined epidemiological data obtained from 498 women aged 20–50 year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented.

Results

After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1–7.8, p = 0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p = 0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking.

Limitations

This study is cross-sectional, which precludes any determination regarding the direction of the relationships.

Conclusions

These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders.

Introduction

Mood disorders are highly prevalent. The lifetime prevalence in Australian women has been estimated to be approximately 30% (Williams et al., 2010). Contraceptive agents are additionally widely used, with a recent article reporting that 58.9% of women residing in Sweden between the age of 16 and 31 use contraceptive agents (Wirehn et al., 2010). A similar prevalence has been reported in Australia (Duke et al., 2007). With a high risk of both depression and usage of contraceptive agents, it is important to know if there is relationship between the two.

There are many different contraceptive agents available. Combined contraceptive agents containing both estrogen and progestin and progestin-only agents, are the two major categories. Hormonal contraceptive agents are commonly used in birth control and cycle control, are effective, and also easy to use (Wirehn et al., 2010).

In 1970 Brenda Herzberg wrote that “Depression is a known side-effect of oral contraceptive therapy”. However, recent studies have delivered an ambiguous pattern of results. While a review article concluded that there are some psychological benefits of estrogen (Studd and Panay, 2004), other studies describe no clear association between hormonal contraception and mental disorders (Duke et al., 2007, Robinson et al., 2004). From this, it is evident that more studies are needed, in particular to determine whether relationships differ according to type of contraceptive agent used. Earlier studies have not investigated both combined and progestin only contraceptives, investigated the relationships within large randomly selected population based samples of women, included a wide range of likely confounding variables and used valid psychiatric interviews to determine mood disorders. Therefore, the aim of this study was to investigate the association between contraception use and current mood disorders in a representative population-based sample of women.

Section snippets

Participants

This study examined data obtained from women participating in the Geelong Osteoporosis Study (GOS), a large population-based study designed to investigate the epidemiology of osteoporosis, and other health disorders. Originally 1494 women (participation of 77.1%) were randomly recruited from the electoral rolls for the Barwon Statistical Division (south-eastern Australia) between 1994 and 1997 and have since been prospectively followed for a decade (retention 82.1%) (Pasco, 2011).

Of those who

Results

In this sample, 40 (8%) women were diagnosed with a current mood disorder according to the SCID-I/NP. Of this group, 8 (20%) were identified with bipolar disorder, 20 (50%) with MDD, 4 (10%) with minor depression, 7 (17.5%) with dysthymia, and 1 (2.5%) with both MDD and dysthymia. Characteristics of those with and without a current mood disorder are given in Table 1. Those with a current mood disorder were more inactive, had a significantly higher number of medical conditions during the past

Discussion

In this cross-sectional, population-based study of women, we report that current progestin-only contraceptive users had a three fold increased risk of a current mood disorder, compared to non-progestin users. In contrast, those currently using combined contraceptive agents were at decreased risk of a current mood disorder compared to non users. These associations were independent of sociodemographic characteristics, medical conditions, medication use and other lifestyle factors.

In one of the

Conclusion

In conclusion, this study suggests that women taking progestin-only contraceptive agents have an increased likelihood of current mood disorders, whereas the use of combined contraceptive agents appeared protective against these disorders. Because of the potential adverse effect progestin-only agents have on current mood, caution should be taken when prescribing these agents to women. If clinically indicated, the combined contraceptive agents appear preferable in terms of mood endpoints.

Role of funding source

The funding providers played no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or in preparation, review, or approval of the manuscript.

Conflict of interest

Gjertrud Svendal has no conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.

Lana Williams has received Grant/Research support from Eli Lilly, Pfizer, The University of Melbourne, Deakin University and the NHMRC.

Julie Pasco has received speaker fees from Amgen, Eli Lilly and Sanofi-Aventis and funding from the Geelong Region Medical Research Foundation, Barwon Health, Perpetual

Acknowledgments

The study was funded by the National Health and Medical Research Council of Australia (NHMRC).

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Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis
2024, Frontiers in Neuroendocrinology
Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.
The influence of health care utilization on the association between hormonal contraception initiation and subsequent depression diagnosis and antidepressant use
2020, Contraception
Citation Excerpt :
In 1971, depression was declared a known side effect of oral hormonal contraceptives [3] and changes in mood are listed as a possible adverse effect of most hormonal contraceptives on the market today [4]. Prospective research studies have been heterogeneous, demonstrating decreased risk [5–7], no association [8–11], and increased risk [12,13] between hormonal contraceptive use and mood symptoms. Population-based studies, on the other hand, have demonstrated a consistent relationship of hormonal contraceptive use with depression and antidepressant use [14,15].
Assess the influence of healthcare utilization on previously reported associations between contraception initiation, diagnosis of depression, and dispensing of antidepressant medications.
Retrospective cohort analysis of insurance records from 272,693 women ages 12–34 years old enrolled in the United States Military Healthcare System in September 2014 and followed for 12 months. We compared outcomes of women who initiated hormonal contraception with all women eligible for care and then with women who accessed care during the study month using Kaplan-Meier and Cox proportional hazards analyses.
Women age 12–34 who initiated hormonal contraception experienced a higher risk of depression diagnosis and antidepressant use when compared to all enrolled women but not when compared to women who accessed care. Among those who accessed care, some progestins (i.e., levonorgestrel, Hazard Ratio (HR) = 1.46, and norelgestromin, HR = 1.93) were associated with an increased rate of depression diagnosis but not antidepressant use; norethindrone (HR = 0.21) was associated with a decreased rate of depression diagnosis.
When compared to women utilizing their health insurance, associations between initiating hormonal contraception and depression diagnosis and antidepressant use decreased or disappeared. This suggests that healthcare utilization may have confounded previous reports of an association between hormonal contraception use and depression and antidepressant use.
Hormonal Contraception and Female Sexuality: Position Statements from the European Society of Sexual Medicine (ESSM)
2019, Journal of Sexual Medicine
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Weight gain as a side effect of POCs has been debated.40,41 An increased likelihood of mood disorders for POC users has been disputed, as well.42,43 SHBG levels decreased slightly during oral LNG contraception, which might be in part responsible for an increased risk for the occurrence of acne.
Hormonal contraception is available worldwide in many different forms. Fear of side effects and health concerns are among the main reasons for not using contraceptives or discontinuing their use. Although the safety and efficacy of contraceptives have been extensively examined, little is known about their impact on female sexual function, and the evidence on the topic is controversial.
To review the available evidence about the effects of hormonal contraceptives on female sexuality in order to provide a position statement and clinical practice recommendations on behalf of the European Society of Sexual Medicine.
A comprehensive review of the literature was performed.
Several aspects of female sexuality have been investigated, including desire, orgasmic function, lubrication and vulvovaginal symptoms, pelvic floor and urological symptoms, partner preference, and relationship and sexual satisfaction. For each topic, data were analyzed according to the different types of hormonal contraceptives (combined estrogen-progestin methods, progestin-only methods, and oral or non-oral options).
Recommendations according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence criteria and specific statements on this topic, summarizing the European Society of Sexual Medicine position, were developed.
There is not enough evidence to draw a clear algorithm for the management of hormonal contraception-induced sexual dysfunction, and further studies are warranted before conclusions can be drawn. A careful baseline psychological, sexual, and relational assessment is necessary for the health care provider to evaluate eventual effects of hormonal contraceptives at follow-up.
All studies have been evaluated by a panel of experts who have provided recommendations for clinical practice.
The effects of hormonal contraceptives on sexual function have not been well studied and remain controversial. Available evidence indicates that a minority of women experience a change in sexual functioning with regard to general sexual response, desire, lubrication, orgasm, and relationship satisfaction. The pathophysiological mechanisms leading to reported sexual difficulties such as reduced desire and vulvovaginal atrophy remain unclear. Insufficient evidence is available on the correlation between hormonal contraceptives and pelvic floor function and urological symptoms.
Both S, Lew-Starowicz M, Luria M, et al. Hormonal Contraception and Female Sexuality: Position Statements from the European Society of Sexual Medicine (ESSM). J Sex Med 2019;16:1681–1695.
Effectiveness and use of hormonal contraceptives (except for intrauterine devices): CNGOF Contraception Guidelines
2018, Gynecologie Obstetrique Fertilite et Senologie
Les contraceptions hormonales restent parmi les méthodes les plus utilisées par les femmes. L’objectif de cette revue est de faire un état des lieux sur l’efficacité et les modalités d’utilisation de ces différentes méthodes. Par ailleurs, certains effets secondaires sont craints et/ou fréquemment rapportés par les utilisatrices de contraceptions hormonales : métrorragies, acné, migraines cataméniales, prise de poids, troubles de la libido et de l’humeur. Dans cette revue de littérature, l’imputabilité des contraceptions hormonales sur la survenue de certains de ces effets secondaires a été discutée et une stratégie de prise en charge de ces derniers a été proposée.
Hormonal contraceptives remain among the most popular methods used by women. The purpose of this work is to review the effectiveness and use of these different methods. In addition, some side-effects are feared and/or frequently reported by users of hormonal contraceptives: unscheduled bleeding, acne, catamenial migraines, weight gain, libido and/or mood disorders. In this review of the literature, the accountability of hormonal contraceptives for the occurrence of some of these side-effects was discussed and a management strategy was proposed.
Oral contraceptives positively affect mood in healthy PMS-free women: A longitudinal study
2017, Journal of Psychosomatic Research
Citation Excerpt :
Thus, OC-users tended to score lower on outcomes associated with reproductive depression than NC women. This effect has been observed previously in both healthy and clinical samples (e.g. [51,59,60,62].). Although women below the age of 20 may be more susceptible to negative mood effects following OC use [38,42,54], we did not observe this in our sample (mean age 20,6).
Menstrual cycle phase and oral contraceptives (OC) use influence mood and cognition and these effects may be moderated by the mineralocorticoid receptor (MR) genotype. The effect of menstrual cycle phase on mood may be increased if participants know that this is the focus of study. We assessed aspects associated with reproductive depression such as mood, interpersonal sensitivity, affect lability and depressive cognitions in MR-genotyped OC-users and naturally cycling (NC) women in a carefully masked design.
A homogenous sample of healthy, PMS-free, pre-menopausal MR-genotyped women (n = 92) completed online questionnaires eight times during two consecutive cycles.
The masking of the research question was successful. OC-users did not differ significantly from NC women in positive and negative affect at the time of assessment, personality characteristics (e.g. neuroticism) or mental and physical health. Both groups reported more shifts in anger in the first cycle week (p < 0.001; η_p² = 0.08). Compared to NC women, OC-users reported fewer mood-shifts between depression and elation in the mid-luteal phase of the menstrual cycle (p = 0.002; η_p² = 0.10) and had fewer ruminating thoughts at all phases (p = 0.003; η_p² = 0.11). Effects of MR-genotype were not significant after correction for multiple comparisons.
OC users scored more favorably on measures associated with reproductive depression. OC users also showed a decreased affect variability possibly indicating an emotional blunting effect, which is in line with previous reports on affect-stabilizing effects of OC. Limitations were loss of cases due to irregularities in the menstrual cycle length and possible confounding by the ‘survivor effect’, since almost all OC-users took OC for more than a year.
The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity
2017, Hormones and Behavior
Citation Excerpt :
Furthermore, COC with an androgenic progestin component (e.g., levonorgestrel) produced more negative effects on mood and emotional well-being than COC containing anti-androgenic progestins (e.g., drospirenone or dienogest; Sundström-Poromaa and Segebladh, 2012). Nevertheless, recent findings also stress that the majority of COC users do not experience overall decreases in mood (Böttcher et al., 2012; Duke et al., 2007; Toffol et al., 2012) with some studies also reporting beneficial effects (Cheslack-Postava et al., 2015; Oinonen and Mazmanian, 2002; Svendal et al., 2012). Although the majority of COC users do not report mood worsening, subtle effects of COC on affective processing have been found in a number of paradigms.
Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing.

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Brief reportThe use of hormonal contraceptive agents and mood disorders in women

Abstract

Background

Methods

Results

Limitations

Conclusions

Introduction

Section snippets

Participants

Results

Discussion

Conclusion

Role of funding source

Conflict of interest

Acknowledgments

Contraception

Journal of Science and Medicine in Sport

Contraception

Medical Hypotheses

Obstetrics and Gynecology

Brain Res.

Molecular Brain Research

Journal of Affective Disorders

Maturitas

NAMS/Solvay Resident Essay Award. Relationship between estrogen, serotonin, and depression

Menopause

Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome

Psychosomatic Medicine

Platelet glutamate receptor supersensitivity in major depressive disorder

Clinical Neuropharmacology

Brief report
The use of hormonal contraceptive agents and mood disorders in women