May 31, 2021
Factors Contributing to a Suboptimal Luteal Phase: A Research Review
By Lucy Teresa Shum Sin, MD
Editor’s Note: A short luteal phase has significant implications for a woman’s fertility and is associated with early pregnancy loss and infertility. Dr. Shum Sin reviewed a 2018 research article[i] by Abdulla et al titled, “Hormonal predictors of abnormal luteal phases in normal cycling women.” The study sheds light on the importance of normal follicular development, ovarian follicle size, and a healthy hormonal milieu to support a normal luteal phase.
Society often defines a health condition in absolute terms—normal vs. abnormal. Yet, in the case of the menstrual cycle, research suggests the difference between normal and abnormal lies within a continuous spectrum. The 2018 observational study by Abdulla et al summarized below focuses on the luteal phase, which is the post-ovulatory phase of the menstrual cycle. The researchers evaluated which preovulatory, periovulatory, and luteal phase characteristics could result in the suboptimal luteal phase found in some women with normal menstruation.
The data derived from a large observational study conducted between 1996 and 1997 in eight natural family planning clinics in Belgium, France, Germany, Italy, and Spain. The study collected daily urine hormone measurements with ultrasound-confirmed ovulation days from 107 women and 326 menstrual cycles. After inclusion criteria, 99 women and 266 menstrual cycles were retained.
The following inclusion criteria were used: (1) age 19-45, (2) menstrual cycle lasting 24-34 days, and (3) no history of anovulatory cycles, infertility, active hormonal treatment for infertility in the past 3 months, oral contraception/hormonal therapy in the past 3 months, abnormal cycles, hysterectomy, tubal ligation, pelvic inflammatory disease, runners, or breastfeeding/postpartum mothers less than 3 months. Ovarian ultrasounds were performed on the first day of observed cervical mucus or when an LH surge was detected by the home test kit until the appearance of an image evidence of ovulation (US-DO, ultrasound day of ovulation), at which point the follicle size was measured.
Hormone levels were analyzed in their corresponding follicular phase, periovulatory phase, and mid-luteal phase, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone-3-glucuronide (E1G, a metabolite of estrogen), and pregnanediol-3-alpha-glucuronide (PDG, a metabolite of progesterone). To characterize the luteal phase, the researchers used four outcomes, including (1) short luteal phase < 12 days; (2) low PDG < 10 microgram/mg Cr (suggestive of low progesterone, randomly chosen to include the lowest third of menstrual cycles); (3) normal, then low luteal PDG level; and (4) low, then normal luteal PDG level.
Variables were tested to eliminate any unclear association they had on the outcome. Analysis was done to find a relationship between five general characteristics (current age, age at menarche, sports activity, tobacco use, and body mass index or BMI), pre-ovulatory characteristics (length and level of the four hormones previously mentioned), peri-ovulatory characteristics (small maximum follicle size and level of the four hormones), and the quality of the luteal phase, as described above.
After variables were adjusted, a short luteal phase was 1.5 times more likely in cycles with a long pre-ovulatory phase and in the presence of an elevated PDG level in the periovulatory phase (p < 0.05). The risk of low PDG in the mid-luteal phase was 2/3 less likely when the periovulatory phase had a high level of PDG. The pattern of a normal PDG level followed by a low PDG level in the mid-luteal cycle was 2-3 times more frequent in the presence of small maximum follicle size and a high PDG level during the periovulatory phase. The pattern of low, then normal PDG level in the mid-luteal cycle was 3/4 less frequent when the periovulatory phase had a high PDG level.
Before variable adjustments, it is worth noting that a high BMI, early menarche, and a low PDG during the follicular phase were significantly associated with a low PDG level in the mid-luteal cycle (p < 0.05).
The results of this observational study suggest the following:
- Factors that contribute to luteal phase deficiency are the same factors that result in a normal average cycle with a suboptimal luteal phase.
- Abnormal luteal phases are reflections of abnormal follicular development as demonstrated by the small maximum follicle size.
- Low, then normal PDG pattern is considered a normal regulation process, as it is associated with lower levels of PDG.
- A high level of PDG during the ovulation phase is more often found in the presence of a short luteal phase.
- Higher BMI is often found with low PDG levels.
This study confirms that a short luteal phase originates from suboptimal follicular development. Hence, treating and supporting the ovulation process during the follicular phase will likely improve, if not resolve, the luteal phase deficiency.
This is vital, since the luteal phase is an essential part of the menstrual cycle that, when abnormal and short, results in repetitive pregnancy loss and infertility.
This is the case in polycystic ovarian syndrome (PCOS), the most common cause of female infertility that is associated with luteal phase deficiencies.
The future looks bright. Given the knowledge gained, it makes sense to study possible interventions to prolong the luteal phase, such as human chorionic gonadotropin (HCG) treatment or progesterone supplementation. It would be beneficial to create an algorithm to guide clinicians in the evaluation and management at different point in the menstrual cycle. Further research on environmental factors, such as estrogen levels in water for consumption, could elicit other elements affecting follicular development, since no relationship was found between small maximum follicle size and short luteal phase or low mid-luteal phase PDG when regression was adjusted for the general characteristics of the participants.
Another study could focus on the association between a high level of PDG during ovulation and a short luteal phase and normal, then low progesterone level. Of similar interest, an investigation of the relationship between BMI and luteal phase characteristics would be enriching to this field, especially when the global population BMI is on the rise.
The menstrual cycle functions as a continuum, with characteristics of each phase impacting the others. It is essential to conduct further research to better understand its intricate composition to improve women’s fertility and reproductive health.
[i] Abdulla, S.H., Bouchard, T.P., Leiva, R.A., Boyle, P., Iwaz, J., Ecochard, R. (2018). Hormonal predictors of abnormal luteal phases in normal cycling women. Frontiers in public health. 6:144. doi: 10.3389/fpubh.2018.00144.
About the Author
Lucy Teresa Shum Sin, MD
Lucy Teresa Shum Sin, MD completed her medical degree at McGill University and is a resident in family medicine at the University of Ottawa. During the FACTS elective, she discovered women’s fertility and reproductive health through the lens of menstrual charting while making connections to the clinical and physiological knowledge gained throughout her medical training. She looks forward to integrating this information into her practice of medicine.
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The FACTS 4-part CME Course – Fertility Awareness Based Methods (FABMs) for Family Planning and Restorative Reproductive Women’s Healthcare prepares you as a medical professional to present more comprehensive options for family planning and women’s health monitoring and management of a range of reproductive health concerns. Through online lectures, live case study discussions, and readings, this course will explore the broad applications of modern Fertility Awareness-Based Methods (FABMs) and their role in pregnancy prevention, infertility, and women’s health.
The course is divided into four parts; you may elect to do any or all of them and they may be completed in any order. Each part is worth up to 14 AAFP-approved CME credits.
In Part A, An Introduction to Modern FABMs for Family Planning, participants will survey modern evidence-based FABMs, including the research underlying the development of the different methods, their effectiveness rates to prevent pregnancy, and the benefits and challenges of using each method. Participants may engage in live case-based discussions to learn how to read the charts of various FABMs.
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