Impact of OC-Induced Mood Lability on Treatment Adherence in Endometriosis

Depression and emotional side effects are major barriers to sustained contraceptive use in endometriosis.

Key Points

Highlights:

• Mood lability and depression are important side effects of oral contraceptives (OCs), particularly progestin-only pills, in women with endometriosis.
• These side effects significantly contribute to treatment discontinuation in this population.

Importance:

• Women with endometriosis have a higher baseline prevalence of depression.
• OC-induced mood symptoms may exacerbate underlying psychiatric vulnerability and reduce treatment adherence.

What's done here:

• Dr. Cevik and Dr. Taylor from the Yale School of Medicine conducted a retrospective study on women with endometriosis who were prescribed combined or progestin-only OCs between 2012 and 2024.
• The primary outcome was OC discontinuation due to mood lability or depression.
• The secondary outcome assessed whether patients with pre-existing depression were more likely to discontinue OCs.
• The total cohort included 2,682 women aged 18–45 with a diagnosis of endometriosis.

Key Results:

• Among 2,682 women, 2,006 were OC users (1,462 combined, 544 progestin-only) and 676 were non-users.
• Depression was present in 33.6% of the total cohort.
• Overall, 44.2% of OC users discontinued treatment. Among discontinuers:
  • 52.3% cited inadequate symptom relief,
  • 33.9% reported mood lability or depression,
  • 13.8% had other side effects.
• Among those who discontinued due to mood symptoms, 52.7% had a prior diagnosis of depression.
• No significant difference in mood-related discontinuation was found between combined and progestin-only OCs or between progestin types.
• Following OC discontinuation:
  • 19.2% switched to another hormonal therapy, 12.3% opted for nonhormonal alternatives,
  • 29.2% underwent surgery, 39.4% ceased all medical treatment.

Interpretation and Critical Context

• A recent letter by Salmeri, Cipriani, and Vercellini  questioned the generalizability of the findings, as the study was based in a single tertiary referral center.
• The reported depression rate in OC users (37.8%) was higher than in large-scale international studies, suggesting potential selection bias or severity differences.
• A higher proportion of OC users underwent surgery (56%) compared with non-users (32%), indicating possible confounding by symptom severity.
• The study did not report hormone dosages, OC regimen types (cyclic vs. continuous), or rates of amenorrhea, all of which may affect both mood and symptom control.
• The use of estrogen-progestins in both OCs and as add-back therapy with GnRH analogs raises questions about the consistency of treatment approaches in managing mood symptoms.

Lay Summary

From the Editor-in-Chief – EndoNews

This study sheds light on an often-overlooked dimension of endometriosis management—the psychological burden associated with hormonal therapy. It underscores the urgent need for personalized care that addresses not only physical symptoms but also emotional well-being. While subsequent commentary has raised important methodological considerations, the findings nonetheless reinforce the importance of emotionally responsive, individualized treatment strategies.

Lay summary

Endometriosis is associated not only with chronic pelvic pain, dyspareunia, dyschezia, dysmenorrhea and infertility but also with a significantly increased risk of mood disorders,anxiety and particularly depression. The global depression rate of women in the reproductive period is between 4.5% and 7%, but for women are diagnosed with endometriosis  this is higher. Oral contraceptives (OCs), including combined estrogen-progestin and progestin-only pills, are commonly prescribed to manage endometriosis-related symptoms. However, emerging evidence suggests that OCs may contribute to mood lability and exacerbate underlying psychiatric symptoms in some patients.

In a recent retrospective cohort study conducted at Yale School of Medicine, Dr. Cevik and Dr. Taylor examined 2,682 women with endometriosis to assess the role of mood-related side effects in OC discontinuation.

Among OC users, 33.6% had a documented diagnosis of depression, and 33.9% of those who discontinued treatment cited mood lability or depression as the primary reason. No significant differences were observed between combined and progestin-only formulations in terms of mood-related adverse effects.

The authors concluded that for patients with endometriosis who are at risk of mood disorders—or who develop such symptoms while on OCs—alternative hormonal or non-hormonal therapies may be warranted earlier in the treatment course.

In response, a commentary by Salmeri, Cipriani, and Vercellini highlighted several important limitations. These included the single-center design, higher baseline symptom severity among OC users which is reflected in higher surgical rates, and lack of detail on treatment protocols such as cyclic vs. continuous pill use or achievement of amenorrhea. The commentators also questioned the suggestion to prefer GnRH analogs, as these regimens also involve hormonal components and may not avoid mood-related risks.

Taken together, this study and its subsequent critique underscore the need for individualized treatment planning in endometriosis—taking into account both somatic and psychological factors when prescribing hormonal therapy.

Research Source: https://pubmed.ncbi.nlm.nih.gov/40021037