By: Kyrie Cassin

Editor’s Note: Below is the summary of a narrative review published in 2019 in Therapeutic Advances in Psychopharmacology by González-Rodríguez and Seeman. [1] Their goal was to summarize the recent literature published on the use of antipsychotics and hormones (estrogen and oxytocin in particular) for use postpartum and during menopause. In her synopsis of their article and findings, Kyrie Cassin added the potential use of fertility awareness-based methods (FABMs) in these patients and the need for future research to incorporate these versatile methods. A DO medical student, Cassin wrote this summary while enrolled in the FACTS elective for medical students. Follow the link to learn more about our new resident elective, which includes training in FEMM or NeoFertility!  And on that note, join us for our LIVE NeoFertility-FACTS Summer Cohort class beginning Wednesday, May 14th.  Registration closes THIS Friday, May 9th, so don’t delay, register today!

Introduction

In their article [1] published in 2019, González-Rodríguez and Seeman sought to provide a summary of current research (2009-2019) on the relationship between antipsychotics and hormones (estrogens and oxytocin in particular) used postpartum or during menopause. The intersection of hormonal changes, mental distress, and the use of antipsychotic agents raised questions for the authors, including the following:

1. Does hormone replacement work and, if so, for which symptoms?
2. Is hormone replacement able to reduce the dose of antipsychotics?
3. Are some antipsychotics more compatible with adjunctive hormones than others?
4. Are hormone-antipsychotic combinations safe and well tolerated and, if so, within what dose range?

Through this literature review and subsequent research, the authors continue to address these and other questions highly relevant to women’s health.

Methodology

For their review, the authors examined the clinical literature from the last decade on the use of estrogens and oxytocin in the postpartum period and during menopause. This included efficacy, safety, and tolerability of hormonal treatments in conjunction with antipsychotics in studies over the same time period. They defined postpartum psychotic disorders carefully, dividing them into mania/mixed episodes with psychotic features; depressive episodes with psychotic features; and nonaffective psychotic episodes.

“For their review, the authors examined the clinical literature from the last decade on the use of estrogens and oxytocin in the postpartum period and during menopause … (including) efficacy, safety, and tolerability of hormonal treatments in conjunction with antipsychotics.”                       

Results

Postpartum

The authors reviewed several studies that used supplemental estrogens to treat or prevent postpartum psychosis. They also reviewed the postpartum use of gonadal hormones to treat nonpsychotic illness, and concluded the utility of hormone treatment is not well justified across several studies. A few oxytocin studies regarding postpartum psychoses are mentioned but have not been replicated to verify their results. Selective estrogen-receptor modulators (SERMs) have not been tested in postpartum disorders.

On the other hand, antipsychotics have been shown to be highly effective to prevent symptom recurrence in women with defined psychotic illness or prior postpartum psychoses. The authors found that hormone adjuncts may depend on the antipsychotic being used.

The authors mentioned the treatment of psychosis with antipsychotics in conjunction with hormones such as progesterone, neurosteroids, luteinizing hormone (LH), and melatonin, with mixed results. For example, the long-acting progestogen contraceptive norethisterone enanthate has been found to increase the risk of postpartum depression when given in the postpartum period.

“The long-acting progestogen contraceptive norethisterone enanthate has been found to increase the risk of postpartum depression when given in the postpartum period.”

Menopause

The authors noted menopause can worsen existing psychotic symptoms, while antipsychotic treatment can aggravate some symptoms of menopause. They detailed the use of estrogen and SERMs (raloxifene) as adjuncts to antipsychotics, and found them to be superior to placebo when treating total psychotic symptoms (excluding affective symptoms or cognitive function). Again, the authors question whether estrogen response is related to the specific antipsychotic the patient is taking. Oxytocin was mentioned in the context of postmenopausal treatment but has not been specifically studied.

Discussion

Although their use remains controversial, estrogens have been considered as adjunctive therapy alongside antipsychotics in the treatment of postpartum psychoses. Estrogens and SERMs have been used successfully to treat psychosis in menopausal and postmenopausal women.

“Estrogens and SERMs have been used successfully to treat psychosis in menopausal and postmenopausal women.”

Regarding oxytocin, this review confirms that research into its role in the treatment of postnatal and menopause-related psychosis is limited. More studies are needed regarding hormonal and biofeedback mechanisms as well as specific doses, timing, and route of intervention when treating psychosis with antipsychotics and hormones. Still, based on available research at the time of their review, the authors argue that such treatment of patients in severe mental distress is safe and can be beneficial.

The authors acknowledge the difficulty in declaring whether hormone replacement, in conjunction with antipsychotics, can improve treatment of psychosis in postnatal or postmenopausal patients. Indeed, a similar review paper published by both authors in 2022 [2] is still seeking answers to similar questions, though they foresee promising routes ahead to continued research into this nuanced area.

In the context of what is taught on the FACTS elective about fertility awareness and FABMs, this study could benefit by also looking at research that incorporates women who track their cycles both for their own awareness and in relation to their fertility. A 2022 literature review by Handy et al [3] showed ample evidence of hormone-related female cycle changes and exacerbation of psychiatric symptoms. Studies focused on the impact of cycle tracking on a patient’s ability to identify and implement strategies to manage symptoms would be an invaluable tool for patients, and may offer an alternative for future treatment. For example, an evidence-based approach to cycle tracking and psychiatric symptom management would be a welcome alternative for women with contraindications to the use of hormones, antipsychotics, or combinations of both.

“Studies focused on the impact of cycle tracking on a patient’s ability to identify and implement strategies to manage symptoms would be an invaluable tool for patients, and may offer an alternative for future treatment.”

The authors assessed the broad effects of hormones as adjuncts to antipsychotics in psychiatric treatment postpartum and during menopause—two distinct groups of patients with different needs and goals for care. Thus, a more detailed literature review with specific suggestions into further research—including the role of FABMs as a potential tool in the management of psychoses—would be of interest to researchers and readers alike.

Editor’s Note: For more articles related to these topics, follow the links below:

• Effects of Steroid Hormones in a Woman’s Brain: A Review
• The Role of Fertility Awareness-Based Methods Postpartum: A Research Review

References

[1] González-Rodríguez A, Seeman MV. The association between hormones and antipsychotic use: a focus on postpartum and menopausal women. Ther Adv Psychopharmacol. 2019 Jul 3;9:2045125319859973. doi: 10.1177/2045125319859973. PMID: 31321026; PMCID: PMC6610461

[2] González-Rodríguez A, Monreal JA, Seeman MV. The Effect of Menopause on Antipsychotic Response. Brain Sci. 2022 Oct 4;12(10):1342. doi: 10.3390/brainsci12101342. PMID: 36291276; PMCID: PMC9599119

[3]  Handy AB, Greenfield SF, Yonkers KA, Payne LA. Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review. Harv Rev Psychiatry. 2022 Mar-Apr 01;30(2):100-117. doi: 10.1097/HRP.0000000000000329. PMID: 35267252; PMCID: PMC8906247

ABOUT THE AUTHOR

Kyrie Cassin
Kyrie Cassin is a fourth-year medical student at Noorda College of Osteopathic Medicine in Provo, Utah. She completed her undergraduate education at Southwestern University in Georgetown, TX, and earned a graduate degree in biomedical science at Drexel University in Philadelphia, PA. She plans to complete residency in emergency medicine and is interested in women’s health, emergency medical services, and social EM. She enrolled in the FACTS elective to learn more about natural family planning methods. She hopes to educate and empower her patients as they make decisions about their healthcare and fertility.

Inspired by what you read?

You can support the ongoing work of FACTS here. To connect with a member of our team, please email development@factsaboutfertility.org. Interested in becoming an individual or organizational member? You can learn more and register here. To discuss with a member of our team, please email membership@factsaboutfertility.org.