Depression as a side effect of the contraceptive pill
Millions of women worldwide use the combined oral contraceptive pill as an effective form of contraception. However, the focus on its side effects to date has mainly been on physical aspects, even though the most commonly stated reason for discontinuation is depression. There are surprisingly few large studies investigating depression related to oral contraceptive use. A pilot study was conducted showing that women using the combined oral contraceptive pill were significantly more depressed than a matched group who were not. More research is needed to better inform women and doctors about depression related to oral contraceptive use, and clinical guidelines are needed regarding the different types of oral contraceptives and their potential depressogenic properties.
[Show abstract] [Hide abstract] ABSTRACT: Rationale: The processing of emotional information is affected by menstrual cycle phase and by the use of oral contraceptives (OCs). The stress hormone cortisol is known to affect emotional information processing via the limbic mineralocorticoid receptor (MR). Objectives: We investigated in an exploratory study whether the MR-genotype moderates the effect of both OC-use and menstrual cycle phase on emotional cognition. Methods: Healthy premenopausal volunteers (n = 93) of West-European descent completed a battery of (emotional) cognition tests. Forty-nine participants were OC users and 44 naturally cycling, 21 of whom were tested in the early follicular (EF) and 23 in the mid luteal (ML) phase of the menstrual cycle. Results: In MR-haplotype 1/3 carriers, ML women gambled more than EF women when their risk to lose was relatively small. In MR-haplotype 2, ML women gambled more than EF women, regardless of their odds of winning. OC-users with MR-haplotype 1/3 recognized fewer facial expressions than ML women with MR-haplotype 1/3. Conclusion: MR-haplotype 1/3 carriers may be more sensitive to the influence of the female hormonal status. MR-haplotype 2 carriers showed more risky decision-making. As this may reflect optimistic expectations, this finding may support previous observations in female carriers of MR-haplotype 2 in a naturalistic cohort study.0Comments 0Citations
- "MR-haplotype status is also associated with the effect of hormones on cognition, particularly the processing of emotionally relevant information: OC users with MR-haplotype 1 or 3 recognised more sad and fearful faces and performed better in the recall of negative characteristics, whereas MR-haplotype 2 carriers did not (Hamstra et al., 2015). The observed differences in sensitivity between different MR-haplotypes may also explain why some women experience depression-like side effects of OCs whereas others do not (Boron and Boulpaep, 2012; Gingnell et al., 2013; Kulkarni, 2007; Poromaa and Segebladh, 2012). In the present study we investigated the influence of OCs and menstrual cycle phase on emotion cognition in MR-genotyped healthy female volunteers. "
[Show abstract] [Hide abstract] ABSTRACT: Hormonal contraceptives are on the market for more than 50 years and used by 100 million women worldwide. However, while endogenous steroids have been convincingly associated with change in brain structure, function and cognitive performance, the effects of synthetic steroids contained in hormonal contraceptives on brain and cognition have barely been investigated. In this article we summarize the sparse findings, describing brain structural, functional and behavioral findings from the literature and suggest that synthetic steroids may contribute to masculinizing as well as feminizing effects on brain and behavior. We try to identify methodological challenges, explain, how results on endogenous steroids may transfer into research on hormonal contraceptives and point out factors that need to be controlled in the study of hormonal contraceptive dependent effects. We conclude that there is a strong need for more systematic studies, especially on brain structural, functional and cognitive changes due to hormonal contraceptive use. The hormonal contraceptive pill is the major tool for population control. Hence, such behavioral changes could cause a shift in society dynamics and should not stay unattended.0Comments 7Citations
- "Reports on OC-related mood changes are inconsistent, ranging from beneficial in most women (Oinonen and Mazmanian, 2002) to increased rates of depression, anxiety, fatigue, neurotic symptoms, compulsion and anger (Robinson et al., 2004; Kulkarni, 2007). Repeated findings of beneficial mood changes may however be biased by data sampling. "
[Show abstract] [Hide abstract] ABSTRACT: Allopregnanolone is a neurosteroid involved in depression, memory, social, and sexual behavior. We have previously demonstrated that treatment with a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds frequently used in hormonal contraception, decreased brain allopregnanolone concentrations. These changes may contribute to some of the emotional and sexual disorders observed in hormonal contraceptive users. We thus examined whether the reduction in allopregnanolone concentrations induced by long-term EE/LNG administration was associated with altered emotional, learning, social, and sexual behaviors. Rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to behavioral tests 24 h after the last administration. EE/LNG treatment reduced immobility behavior in the forced swim test, without affecting sucrose preference and spatial learning and memory. In the resident-intruder test, EE/LNG-treated rats displayed a decrease in dominant behaviors associated with a reduction in social investigation. In the paced mating test, EE/LNG treated rats showed a reduction in proceptive behaviors, while the lordosis quotient was not affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats increased sexual activity and cerebrocortical allopregnanolone concentrations. Prior administration of finasteride decreased allopregnanolone concentrations and abolished the increase in proceptivity induced by progesterone administration. The decrease in brain allopregnanolone concentrations induced by EE/LNG treatment is associated with a reduction in social behavior and sexual motivation in female rats. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.0Comments 3Citations
- "We hypothesized that the neurochemical changes induced by EE/LNG treatment may contribute to some of the emotional disorders observed in hormonal contraceptive users. In fact, several studies demonstrated that hormonal contraceptives might have a negative effect on anxiety, mood, and emotional well-being in women (Bottcher et al. 2012; Hall et al. 2012; Kulkarni 2007; Kurshan and Epperson 2006; Oinonen and Mazmanian 2002; Segebladh et al. 2009; Welling 2013). In addition, some studies have focused on effects of hormonal contraceptives on women's libido and sexual adaptations. "