Prior to puberty, the rate of mood disorders in males and females is roughly the same; however in adolescence, depression doubles in (biological) girls. While the association isn’t clear, it is reasonable to consider that hormones may be involved, at least for some. For instance, we know that menstrual cycle–related mood changes have been noted since the time of Hippocrates. In this article, I will discuss premenstrual dysphoric disorder (PMDD), as well as potential mood-related side effects of hormonal contraceptives. Because I am talking about physiology, I will be referring to individuals born as biological females in the absence of any hormonal gender treatments, regardless of identified gender.
Many young women will acknowledge somatic and/or psychological symptoms that occur in the luteal phase of their cycle, most commonly in the week before menses begins. The most common somatic symptom is bloating, and mood symptoms are irritability and mood lability.1 To meet criteria for premenstrual syndrome (PMS), a woman must endorse one symptom that causes impairment in their functioning and reoccurs over consecutive cycles. PMDD is more specific and involves five or more affective symptoms, at least one of which is consistent with depressed mood, irritability, anxiety, or mood lability. The other potential symptoms include impaired concentration, fatigue, insomnia or hypersomnia, anhedonia, and appetite issues, all of which are included as criteria for major depression. The population prevalence has been quoted between 2% and 5% and is relatively stable across cultures.1 It tends to be highly genetic, as well as highly comorbid with other psychiatric disorders.2 Girls and women with higher rates of trauma appear to be more likely to experience symptoms,3 which indicates there are environmental influences that can interact with genetic vulnerability.
Interestingly, studies have not found differences in serum hormone levels between those with PMDD and others, which leads to the hypothesis that the main difference is in a woman’s sensitivity to circulating hormones,4 and there has been some evidence of different concentrations of neurotransmitters between affected and unaffected women. Many hormone-neurotransmitter interactions have been described, but two that have received the most attention include the relationship between progesterone, its main metabolite allopregnanolone, and gamma-aminobutyric acid (GABA) receptors. Allopregnanolone, which interacts with GABA receptors similarly to benzodiazepines, tends to be higher in the luteal phase, rising with progesterone, and the concentration quickly recedes at the onset of menses as progesterone levels drop off. The other highly notable relationship is the positive association between estradiol and the expression of the serotonin transporter (SERT) genes, which can potentially lead to higher levels of circulating serotonin in the follicular phase.
When PMDD is suspected in an adolescent who presents with intermittent mood and anxiety symptoms that lessen or disappear at baseline and appear unrelated to circumstances, it is important to check in regarding monthly patterns. It can be challenging for adolescents to make this connection, and even more so prior to achieving cycle regularity. Observational studies suggest that by age 14 years, about 82% of girls have a regular cycle.5 The best way to help a patient make the connection is to suggest a period tracking app on their smartphone or tablet. There are many available period trackers that track mood as well and are free to download. Sometimes, simply the act of tracking and bringing awareness to the pattern is therapeutic in itself; sometimes, more formal treatment is needed.
Once the diagnosis of PMDD has been established, there are several options for treatment that range from supplements and herbal remedies to SSRIs, as well as psychotherapy. Treatment may begin with calcium supplements (1,200 mg have been effective in reducing symptoms)6 and referral for cognitive-behavioral therapy (CBT). CBT appears to be associated with a shift in the ability to attribute symptoms to hormones,7 which can help decrease hopelessness and reactivity. SSRIs are another effective strategy to treat PMDD, both taken daily and continuously and also taken in a pulsed fashion, starting with the onset of symptoms or 7-10 days before the period starts and stopping on the first day of menses. Low doses of sertraline, fluoxetine, paroxetine, escitalopram and citalopram have been studied.8 There is some low-quality evidence for herbal supplements as well, probably the most consistent finding is for Vitex taken the week prior to menses.9 Finally, certain oral contraceptives have been associated with PMDD symptom reduction, specifically formulations with 3 mg of drospirenone (a fourth generation progesterone) and 20 mcg of ethinyl estradiol.10 Other formulations, including progesterone-only pills, have not been helpful and have been demonstrated to have a negative effect on mood.11
The literature on hormonal contraceptives and mood can be confusing. While oral agents containing drospirenone have been helpful for premenstrual dysphoria, other studies outside of the PMDD literature have found positive associations between oral contraceptives and depression in adolescents.11 Girls taking combined oral contraceptives seem to be at a 1.8-fold risk of depression, while girls taking progesterone-only formulations were at 2.2 times the risk of developing depression, compared with girls who weren’t taking anything. These days, more pediatricians are recommending long acting reversible contraceptives (LARCs), and there is some thought that even these may carry some risk, but this remains to be studied.
In conclusion,As a provider, you are in a special position to help your patients by bringing nonjudgmental awareness to the potential contribution of their own cyclical hormones or that of exogenous hormones associated with contraceptive choices. Whether it means switching contraceptives, adding calcium or starting a low dose SSRI for 1 week a month, there are many ways to approach symptoms. Often, simply helping make the connection between physiology and mood can be empowering.
Dr. Guth is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and the University of Vermont, both in Burlington. Email her at [email protected].