The Mediterranean Diet and luteal phase deficiency in healthy eumenorrheic women
By: Chantell Melgarejo, DO
Editor’s Note: Changes in a woman’s cycle may result from any number of conditions, from dietary and lifestyle factors to chronic illness. During Crohn’s and Colitis Awareness week, we highlight the complicated research surrounding dietary interventions, exploring the associations between a Mediterranean diet and luteal phase deficiency. The diet is touted as beneficial for many patients, including those with Crohn’s disease. [1] . Former FACTS elective student Chantell Melgarejo summarized research by Andrews et al.[2] that also found an unexpected relationship between the Mediterranean diet and luteal phase deficiency in otherwise healthy, regularly menstruating women.
On a separate note, on behalf of the entire FACTS team, we want to say THANK YOU to everyone who has contributed to our end-of-year giving campaign thus far. We are especially grateful to those of you that made a donation last week in celebration of Giving Tuesday. With your support, we met our matching goal of $5,000. We are so grateful!
Introduction
Luteal phase deficiency (LPD), marked by inadequate progesterone secretion by the corpus luteum, may increase the risk of infertility and early miscarriage. Prior studies have also observed a positive association between LPD and low energy availability. Research suggests that low energy availability caused by overexercise and/or excessive dietary restraint may increase the risk of LPD, placing athletes and women with eating disorders at greater risk for associated adverse pregnancy outcomes. [2] Despite ample research indicating the importance of a healthy lifestyle and diet, less research is available exploring the implications of various dietary factors and trends on clinical pregnancy rates, which raises the question: How does overall diet quality affect a healthy woman with regular menstrual cycles? The study by Andrews et al. explores this concept by examining the association between dietary factors and luteal phase deficiency in healthy, eumenorrheic women, who specifically adopt the popular Mediterranean diet.[2]
“Research suggests that low energy availability caused by overexercise and/or excessive dietary restraint may increase the risk of luteal phase deficiency.”
Methodology
In this study, 259 healthy, regularly cycling women of reproductive age were followed for one or two menstrual cycles. Participants were recruited from western New York with the following parameters in mind: 1) 18 to 44 years old, 2) self-reported menstrual cycles between 21 and 35 days for the past six months, 3) no use of oral contraception or oral hormonal therapy during the past three months, and 4) no pregnancy within the last six months. Participants suffering from chronic illnesses related to diabetes, liver, or kidney diseases were excluded, along with those who had sought out treatment for infertility or gynecological conditions.
At the enrollment visit, participants completed demographic questionnaires and baseline height and weight were recorded. Participants were taught how to use fertility monitors to estimate ovulation and instructed to keep a daily diary to track exercise routines, smoking habits, perceived stress, and fertility monitor results. The fertility monitors tracked urinary hormones, including luteinizing hormone (LH) and estrone 3- glucuronide, to estimate the timing of the LH surge.
Participants reported to the clinic during each phase of their menstrual cycle: menses, mid-follicular, late follicular, LH surge, expected ovulation, early, mid- and late luteal phases. During each visit the participant’s diary and fertility monitor results were reviewed, and blood samples were drawn to measure serum progesterone and LH concentrations. Participants were also required to complete a 24-hour dietary recall at each visit. Food and beverages consumed, macronutrients, micronutrients, and Mediterranean diet score (MDS) were recorded at each visit. High MDS scores demonstrated high compliance to the Mediterranean diet.
All cycles included in the study recorded the complete cycle and were ovulatory. Ovulation was operationalized as reported progesterone levels above 1 ng/ml, preceded by an observed urine or serum LH surge, based on prior models of luteal phase deficiency proposing a 1 ng/ml cutoff to support successful implantation. A cycle was determined to have a luteal phase deficiency if luteal phase duration was less than 10 days and peak luteal progesterone less than or equal to 10 ng/ml.
Linear models were used to chart the data by comparing women with all normal cycles versus women with at least one LPD cycle. A p-value was used to determine significance of the findings.
Results
For the 259 participants, only 463 cycles met criteria for ovulation and were included in the analysis. The average participant was 27-years-old. Most women identified as white and unmarried. Data analysis revealed that age, sexual activity, and the use of hormonal contraceptive were inversely correlated with luteal phase deficiency, whereas vigorous exercise was positively correlated with LPD.
Of the 463 cycles analyzed, 41 cycles met the criteria for LPD. Analysis of dietary data found that participants with LPD reported a higher MDS than those with normal cycles. Higher intakes of vegetable proteins, fiber, fruits and vegetables, vitamin B6 and isoflavone were observed in LPD cycles. Higher levels of selenium, a micronutrient, were observed in normal cycles.
Discussion
Andrews et al. sought to determine the association between dietary factors and luteal phase deficiency in healthy women with eumenorrheic cycles. Specifically, how does a stereotypically “healthy” diet and lifestyle affect a healthy woman’s menstrual cycle? Previous studies have demonstrated an association between a Mediterranean diet and a decreased risk of cardiovascular disease, as well as an increased libido in women diagnosed with metabolic syndrome. However, this particular study sheds light on some potential risks of adhering to the promoted diet; results suggest the Mediterranean diet may negatively impact a healthy woman’s menstrual cycle by increasing the likelihood of luteal phase deficiency.
“Results suggest the Mediterranean diet may negatively impact a healthy woman’s menstrual cycle by increasing the likelihood of luteal phase deficiency.”
The Mediterranean diet is rich in fiber, and the researchers posit that the consumption of higher levels of fiber may negatively alter the reproductive hormone concentrations by changing the pH of the gut bacteria. Altering the microbiome pH may lead to a decrease in serum progesterone hormone reabsorption and thereby increase the risk of anovulation and luteal phase deficiency.
Further studies should investigate this hypothesis within a larger, more diverse sample population; study limitations include limited data and generalizability. The participant population was primarily comprised of white women from western New York. A more racially and geographically diverse cohort, as well as analysis of a larger number of menstrual cycles would shed greater light on the associations observed by Andrews et al.
Reliance on self-reporting by participants also presents challenges. Some women may have had undiagnosed infertility issues prior to the start of the study, which confounds the real incidence of luteal phase deficiency. This demonstrates the importance of fertility awareness-based methods (FABMs) of charting, not only for patients with documented infertility, but also for patients who believe their cycles are normal. Without adequate knowledge of her body’s biomarkers and fertility cycle charts, a patient who identifies as “normal” may not actually have a healthy cycle. Similarly, as this study showed, a Mediterranean diet may not always be a healthy option.
“Without adequate knowledge of her body’s biomarkers and fertility cycle charts, a patient who identifies as “normal” may not actually have a healthy cycle.”
Sources
[1] Papada E, Amerikanou C, Forbes A, Kaliora AC. Adherence to Mediterranean diet in Crohn’s disease. Eur J Nutr. 2020;59(3):1115-1121. doi:10.1007/s00394-019-01972-z
[2] Andrews MA, Schliep KC, Wactawski-Wende J, et al. Dietary factors and luteal phase deficiency in healthy eumenorrheic women. Hum Reprod. 2015;30(8):1942-1951. doi:10.1093/humrep/dev133
ABOUT THE AUTHOR
Chantell Melgarejo, DO
Chantell Melgarejo, DO, is a second-year pediatric resident at Palms West Hospital in Palm Beach, Florida, pursuing a career in pediatric hospitalist medicine. She completed the FACTS elective as a fourth-year medical student at Touro College of Osteopathic Medicine.
