May 1, 2023

Mental Health Awareness Month

The Surprising Dynamics of Luteal Phase Hormones in Premenstrual Dysphoric Disorder

By: Stephanie Wong​

Editor’s Note: To mark Mental Health Awareness Month, we are highlighting research that assessed the relationship between hormone levels and symptoms of premenstrual dysphoric disorder (PMDD). The 2019 study [1] published in the International Journal of Environmental Research and Public Health was summarized by Stephanie Wong while on the FACTS elective. The study highlights the need for further research on ovarian hormone dynamics as they relate to symptom severity in both premenstrual syndrome (PMS) and PMDD. Wong presents a compelling case to include fertility awareness-based methods (FABMs) in future studies to predict the timing of the luteal phase more accurately and lend greater insight to support women with PMDD.

Introduction

Many women who suffer from premenstrual dysphoric disorder, or PMDD, experience debilitating symptoms that can negatively impact their behavioral, physical, and mental health throughout the reproductive years. Symptoms of PMDD typically appear with every ovulatory cycle starting during the latter portion of the luteal phase, and improve after the return of menses. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, PMDD is more severe than premenstrual syndrome (PMS).

Studies have shown that estrogen or progesterone supplementation may reduce symptoms of PMS. Yet, for women diagnosed with PMDD, adding these hormones has a tendency to exacerbate the symptoms of PMDD. In the research study summarized below, Yen et al analyze the specific ovarian hormone dynamics of estrogen and progesterone during the menstrual cycle and study their correlation to PMDD symptoms and symptom severity.

“Studies have shown that estrogen or progesterone supplementation may reduce symptoms of PMS.”

Methodology

In this prospective study, women with untreated PMDD served as volunteers. The control group consisted of other volunteers with less severe symptoms who did not meet the criteria for a diagnosis of PMDD. The final analysis consisted of data collected from 81 women with PMDD and 68 other women who served as the control group. Each woman kept a daily symptom diary to document their PMS-like or PMDD symptoms. They also took a weekly PMDD severity questionnaire (PMDDSQ) as a scale to define symptom severity throughout the study. Estrogen and progesterone levels were sampled during the luteal phase of their menstrual cycles. For this study, the luteal cycle was divided into an Early Luteal (EL) phase and a Late Luteal (LL) phase. The EL phase was defined as the 3-4 days after ovulation as predicted by the previous cycle. The LL phase was defined as the 3 days before the predicted onset of menses in the cycle.

Results

In this study, there was no statistical significance between the progesterone levels in the PMDD group and the control group in either the EL or LL phase. Regarding estrogen levels, the PMDD group had statistically significant lower levels of estrogen than the control group throughout both the EL and LL phases. The lower estrogen levels in the LL phase noted in the PMDD group just barely met the statistically significant criteria. On the other hand, the EL estrogen levels seen in the PMDD group were drastically lower compared to the EL phase estrogen levels of the control group. Individuals with lower estrogen levels in the EL phase were also noted to have more severe symptoms of PMDD.

“The PMDD group had statistically significant lower levels of estrogen than the control group throughout both the early and late luteal phases.”

Further statistical analysis of the estrogen and corresponding progesterone levels revealed an interaction between the two hormone levels in addition to the documented PMDD symptom severity in the study. Additionally, the data from the PMDD participants was divided into lower EL estrogen and higher EL phase estrogen data sets to decipher whether EL phase estrogen levels had a moderating effect on progesterone. Analysis reinforced this, as the data showed that participants with PMDD with lower EL phase estrogen levels also had higher EL phase progesterone levels and corresponding higher severity of symptoms.

Discussion

In previous studies, progesterone supplementation was shown to decrease PMS-like symptoms for patients with PMS, but this same supplementation had an exacerbating effect on the PMDD symptoms in patients with PMDD. The results of this 2019 study present a possible explanation for the difference in response to progesterone supplementation. This study by Yen et al suggests the functional estradiol-progesterone ratio may be a more important factor contributing to PMDD symptoms, as opposed to progesterone or estrogen levels in isolation. The individuals with lower EL phase estrogen and higher EL phase progesterone were more vulnerable to severe PMDD symptoms. Expanding the focus of hormone supplementation beyond progesterone in isolation and including estradiol for a complete estradiol-progesterone ratio combined effect suggests a different approach to helping women suffering from PMDD.

“The individuals with lower estrogen and higher progesterone in the early luteal phase were more vulnerable to severe PMDD symptoms.”

Limitations of this study include the small sample size and subjective reports of symptoms and symptom severity. Also, the luteal phase in the subjects was an estimate based on previous menstrual cycle data. Future studies may predict the timing of the luteal phase with higher precision by tracking the menstrual cycle with a more accurate charting method that incorporates cervical mucus, basal body temperature, and/or urinary hormones. Continued research on the dynamics of ovarian hormones is needed to gain a better understanding of their role in both PMS and PMDD.

Sources

[1] Yen JY, Lin HC, Lin PC, Liu TL, Long CY, Ko CH. Early- and Late-Luteal-Phase Estrogen and Progesterone Levels of Women with Premenstrual Dysphoric Disorder. Int J Environ Res Public Health. 2019;16(22):4352. Published 2019 Nov 7. doi:10.3390/ijerph16224352.

ABOUT THE AUTHOR

Stephanie Wong

Stephanie Wong is a fourth-year medical student at Nova Southeastern University – Dr. Kiran C. Patel College of Osteopathic Medicine in Clearwater, FL. She completed her undergraduate education at the University of Texas in Austin before earning a master’s degree at Drexel University in Philadelphia. She plans to pursue residency training in either physical medicine and rehabilitation or family medicine. She enrolled in the FACTS elective to further her knowledge of women’s health issues as she continues her medical education.