By Valeria Espinoza
Editor’s Note: This is the summary of a committee opinion [1] on the diagnosis and management of luteal phase deficiency. It was published in Fertility and Sterility in 2021 and summarized by Valeria Espinoza while on the FACTS elective in fertility awareness. Women who learn to chart their cycles notice clues to diagnose luteal phase abnormalities earlier, which may help prevent recurrent pregnancy loss and other common women’s health conditions. Learn more about these important topics through the FACTS student elective, the personalized resident elective, the online CME course, and the FACTS fellowship that will launch in the fall of 2026!
Introduction
The luteal phase begins after ovulation and ends before the menstrual period begins. Although its typical length is 12-14 days, it may range from 11-17 days.* The ruptured follicle transforms into the corpus luteum and begins to secrete progesterone. The secretion of progesterone is under the control of luteinizing hormone (LH), which responds to the pulsatile release of GnRH by the hypothalamus. The resulting pulsatile production of LH leads to progesterone levels that may fluctuate significantly, with multiple shifts within a 90-minute window often noted in the mid-luteal phase.
This interplay of hormones causes the endometrium to go from proliferative to secretory — a response which depends on the development of the ovarian follicle, ovulation, and the function of the corpus luteum. Progesterone levels peak 6 to 8 days after ovulation. If implantation occurs, human chorionic gonadotropin (hCG) is secreted and stimulates the corpus luteum to continue producing progesterone. In the absence of hCG, progesterone levels decline.
“Progesterone levels peak 6 to 8 days after ovulation. If implantation occurs, human chorionic gonadotropin (hCG) is secreted and stimulates the corpus luteum to continue producing progesterone.”
Luteal Phase Deficiency
Luteal phase deficiency (LPD) has been described clinically by a length less than 9 to 11 days; biochemically, low progesterone levels persist throughout the luteal phase. Although LPD has been associated with pregnancy loss and infertility, the ambiguity of its definition and diagnosis has limited the number of reliable studies to determine the most effective treatment options.
Still, many conditions are known to affect the pulsatility of GnRH, LH and/or progesterone, and this must be corrected if there is clinical evidence of LPD. Some of these conditions include hypothalamic amenorrhea, eating disorders, stress, excessive exercise, significant weight loss, severe obesity, polycystic ovary syndrome (PCOS), endometriosis, 21-hydroxylase deficiency, thyroid dysfunction, hyperprolactinemia, renal transplantation, elevated beta-endorphin levels, lactation, aging, ovarian stimulation alone, and use of assisted reproductive technology (ART).
LPD has been associated with infertility and subfertility, first-trimester pregnancy loss, short menstrual cycles, and premenstrual spotting, but it has also been diagnosed in women who appear to menstruate normally. LPD can affect endometrial development through several mechanisms:
- Low follicular phase levels of FSH and estradiol, FSH/LH ratios, and FSH and LH pulsatility, leading to low luteal phase levels of estrogen and progesterone
- A deficiency in ovarian hormone production
- Progesterone resistance in the endometrium
- Idiopathic
“Luteal phase deficiency has been associated with infertility and subfertility, first-trimester pregnancy loss, short menstrual cycles, and premenstrual spotting, but it has also been diagnosed in women who appear to menstruate normally.”
Possible Criteria for Diagnosis
Luteal phase length
The average luteal phase length is 14 days with a normal variation of 11 to 17 days.* A short luteal phase has been described with a length of 9 to 11 days. Yet, in some studies, 13% and 18% of cycles had a luteal length of less than 10 and 12 days, respectively, and this did not decrease their fecundity over 12 months.
Progesterone levels
Since progesterone is secreted in pulses, its levels can fluctuate between 5 and 40ng/ml. Studies reveal that luteal progesterone values <5 and <10 occur 8.4% and 31.3% of the time, respectively, which makes a single random measurement difficult to interpret. There is an option to build an integrated progesterone value by measuring daily progesterone and using a percentile of cycles in which <10th percentile (<80ng/ml) has been proposed as a diagnostic test for LPD. If progesterone levels cannot be tested daily, it has been proposed to test on luteal phase days 5 to 9 and diagnose LPD if the sum of all values is below 30.
“Since progesterone is secreted in pulses, its levels can fluctuate between 5 and 40ng/ml … which makes a single random measurement difficult to interpret.”
Progesterone levels & luteal phase length
According to the BioCycle study, LPD can be defined by a mix of clinical (luteal phase <10 days) and biochemical (luteal progesterone levels <5ng/ml) criteria, which were associated with lower follicular estradiol, luteal estradiol and progesterone, as well as lighter menstrual flow. [2]
Endometrial biopsy
The studies that defined the endometrial biopsy result as a diagnostic criterion had done it only with the histology, ignoring that for implantation to happen, other factors should be considered. These factors include steroid receptors, structural proteins, growth factors, cytokines, other receptors, and pinopodes. Furthermore, the endometrium may mature differently depending on the area, which makes a single biopsy an incomplete assessment.
Proposed Treatment Options
When it comes to treatment of LPD, it is necessary to first correct any underlying cause(s) of LPD, such as thyroid abnormalities, hyperprolactinemia, and others listed above. If no specific cause is found, an empiric treatment may be offered, including luteal progesterone, luteal progesterone plus estrogen, luteal hCG, or ovarian stimulation with clomiphene or gonadotropins. Yet, none of these treatments have been demonstrated to treat LPD successfully.
The authors conclude more research is needed to first define luteal phase deficiency better.* This will help determine how to diagnose it, how often it causes infertility and/or early pregnancy loss, and the best treatment options to offer these women and couples.
*Editor’s Note: Although the authors noted the normal length of the luteal phase may range from 11 to 17 days, most studies suggest 16 days is the upper limit of normal. To define luteal phase deficiency more accurately, research should include women who track their cycles. Learn more about the challenges around LPD diagnosis and treatment in these summaries written by students on the FACTS elective:
- Factors Contributing to a Suboptimal Luteal Phase: A Research Review by Dr. Lucy Teresa Shum Sin
- Hormone Profiles and the Luteal Phase: A Review of Research by Estefan Michael Beltran
References
[1] Diagnosis and treatment of luteal phase deficiency: a committee opinion. (2021). Fertility and Sterility, 115(6), 1416–1423. doi:10.1016/j.fertnstert.2021.02.010
[2] Schliep KC, Mumford SL, Hammoud AO, et al. Luteal phase deficiency in regularly menstruating women: prevalence and overlap in identification based on clinical and biochemical diagnostic criteria. J Clin Endocrinol Metab. 2014;99(6):E1007-E1014. doi:10.1210/jc.2013-3534
ABOUT THE AUTHOR
Valeria Espinoza is a fourth-year medical student at La Universidad Latina de Costa Rica in San José, Costa Rica. She plans to pursue residency in obstetrics and gynecology and is passionate about women’s health and the theology of the body. She enrolled in the FACTS elective to gain a better understanding of the female cycle, natural family planning, and innovative ways to manage gynecological problems. She wants to educate her future patients and provide a more integrated approach so they feel more empowered over their health and reproductive decisions.
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