What Do We Need to Learn About Oral Contraceptives?
January 1, 2024
In this Q&A, Elizabeth Hampson, PhD, a professor in the department of psychology and core member of the graduate program in neuroscience at Western University in London, Canada, discussed what is needed in reproductive health research.
CTU: What types of research have been conducted on oral contraceptives (OCs) and central nervous system side (CNS) effects? What more is needed?
Hampson: Most of the data we have so far are based on observational research designs. Often, current users of combined oral contraceptives are simply compared with women not currently using them. There are very few randomized, placebo-controlled designs in this topic area.
Because most of the research into CNS variables is recent, there is a great deal of future research to be done. We hope to see a greater variety of research designs included in future work.
I think a wider variety of CNS variables needs to be considered, and more studies using functional brain imaging would, of course, be instructive. We need to see large-sample studies and research designs that better take into account the differences across brands of pills in ethinyl estradiol dosage, and in the classes and doses of progestins that are used.
All these variables may be pertinent to CNS effects. Duration of use also might be relevant. We also need to know whether any effects are present only for combined oral contraceptives or whether they might be seen for progestin-only hormonal contraceptives as well.
CTU: Some new studies are highlighting the connection between depression and the use of OC (including Julia Gawronska’s study on the association of oral contraceptive pill use and depression among U.S. women). What do clinicians need to know about OC and depression? What can they do to help patients understand how OC pill use may minimize their risk of depression?
Hampson: Over the past five years or so, at least half a dozen large studies have suggested a possible connection between oral contraceptives and depressive-type changes in a subset of users.
Specifically, precipitation of depressive mood changes following the onset of oral contraceptive use. For example, an influential report by Skovlund et al described a prospective cohort study of more than 1 million women based on the national medical records of Denmark.1 Compared with non-users, users of OCs with no prior history of depression showed an elevated risk of first use of antidepressants or first diagnosis of depression following the onset of OC treatment. The odds were highest for adolescents ages 15-19 years and for users of progestin-only contraceptives.
On the face of it, such findings suggest that depression may be an adverse effect of hormonal contraceptive use in a small subset of users. Several further epidemiologic studies have likewise supported a statistical association between depressive changes and OC use during adolescence.
But not all studies suggest increased risk. It may be the case that adolescents, specifically, are vulnerable to these emotional changes, or perhaps that such effects are associated only with certain subclasses of OCs or person-specific risk factors.
In a small archival dataset of our own, consisting of approximately 200 OC users, we saw increased negative affect only among the users of third- and fourth-generation progestins or pills having very low estrogen content.
Until these complexities are sorted out by further research, clinicians might be advised to remain watchful for any negative mood changes that might occur in association with OC use, and if necessary, consider switching those who develop adverse mood changes to an alternative pill formulation.
The emerging picture of mood is complex because there might also be subpopulations of women who can benefit from OC use.
Notably, a few studies have suggested that current OC usage may result in milder premenstrual mood symptoms — in other words, a mood-stabilizing effect — in women who have a history of significant premenstrual dysphoria predating their use of OCs.
CTU: Is there anything else you would like to add about this topic?
Hampson: This topic area is still very new. Although the emerging findings are mixed, we should all keep an open mind to the possibility that OC steroids may have CNS effects, just as their naturally occurring counterparts do. The field of neuroscience over the past 30 years has gained an increased appreciation of the fact that endogenously occurring steroids, such as 17-beta estradiol or progesterone, play important neuromodulatory roles in both female and male brains.
REFERENCE
- Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry 2016;73:1154-1162.
In this Q&A, Elizabeth Hampson, PhD, a professor in the department of psychology and core member of the graduate program in neuroscience at Western University in London, Canada, discussed what is needed in reproductive health research.
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