Urinary Pregnanediol-3-Glucuronide to Confirm Ovulation: A Review
By: Julianne Hall, MD
Director’s Note: This week, we feature research about urinary hormone monitoring reviewed by Dr. Julianne Hall, a former FACTS elective participant. Previous studies discuss the role of urinary hormone assays to assess female health. Some fertility awareness-based methods (FABMs), such as the Marquette Model and FEMM, utilize these biomarkers. Yet, some of them, such as traditional luteinizing hormone (LH) assessments, may present challenges in confirming that ovulation has already occurred. The study by Ecochard et al  summarized below focuses specifically on the diagnostic applications of urinary pregnanediol-3-glucuronide (PDG) to confirm ovulation.
Urinary hormone assays have been utilized for decades to assess women’s reproductive cycles. Some modern fertility awareness-based methods of family planning utilize hormone assays in conjunction with other physiologic biomarkers, such as cervical mucus and basal body temperature (BBT), to identify the fertile phase of the menstrual cycle. For example, the Marquette Model utilizes a urinary hormone monitor that detects estradiol metabolites and LH to identify the opening of the fertile window. However, none of the modern FABMs utilize urinary hormones specifically to identify the end of the fertile window.
“Some modern fertility awareness-based methods of family planning utilize hormone assays in conjunction with other physiologic biomarkers, such as cervical mucus and basal body temperature, to identify the fertile phase of the menstrual cycle.”
Current urinary assays, such as LH kits, are fairly accurate but not 100% effective to confirm ovulation. LH levels often vary in amplitude, duration, and configuration, and these kits may miss ovulation when urinary LH concentrations are above 20 mIU/mL. Given these challenges in the use of urinary LH, reproductive specialists seek to develop more specific, accurate assays. Beyond LH, potential hormones that may be used in such assays include oestrone-3-glucuronide and pregnanediol-3a-glucuronide (PDG).
During a woman’s cycle, progesterone levels increase after ovulation. Several investigators have proposed that a urinary assay detecting metabolites of progesterone may be effective in identifying the start of the post-ovulatory luteal phase, the second half of the cycle in which a woman is no longer fertile. The study by Ecochard et al  summarized below assessed the diagnostic potential of urinary PDG concentrations to confirm ovulation and the start of the luteal phase.
“Several investigators have proposed that a urinary assay detecting metabolites of progesterone may be effective in identifying the start of the post-ovulatory luteal phase, the second half of the cycle in which a woman is no longer fertile.”
The study was a secondary, prospective analysis of an observational study conducted in the mid-nineties in eight fertility centers across Europe. The study group included 107 healthy menstruating women ages 18-45 years old. Women with a history of infertility, pelvic inflammatory disease (PID), cycle disturbances, prior gynecologic surgeries, recent deliveries, current breastfeeding, or current hormonal use were excluded. All participants reported menstrual cycles lasting 24-34 days and had prior experience charting their BBT and cervical secretions. A total of 326 cycles were evaluated.
The study systematically recorded participants’ changes in cervical mucus, transvaginal ovarian ultrasounds, and daily first morning urine (FMU) over hundreds of menstrual cycles. The women assessed their cervical mucus 3 times per day, recording the sensation and consistency. The final day of clear, stretchy, lubricative “fertile” mucus was deemed the “peak day.” Serial transvaginal ovarian ultrasounds with follicle measurements were obtained at the onset of fertile mucus or at detection of the LH surge via hormonal testing.
The ultrasound-determined day of ovulation was the 24-hour period that separated the sight of a mature follicle on ultrasound and one of the following identified on the subsequent scan: (1) a change in follicle size, shape or density, (2) follicle rupture, (3) corpus luteum, or (4) free fluid in the cul-de-sac. Of note, this study defines the fertile phase as the period between the first day of menses to the end of the ultrasound-determined day of ovulation. The infertile phase is defined as the day after ultrasound-confirmed ovulation to the first day of the next menstrual cycle.
Three specific scenarios were tested: (1) use of a daily PDG test alone, (2) use of daily PDG testing after the first positive urinary LH, and (3) use of a PDG test after the disappearance of fertile mucus. The combination of physiologic markers of ovulation with urinary hormone metabolites was utilized, as it could synergistically improve identification of fertile windows. When measuring urinary PDG, two different models were proposed to declare infertility: either one day of PDG positivity or a total of 3 consecutive days of PDG positivity. The three scenarios described above were applied to both models.
Results and implications
The data indicated that after the first positive urinary LH test or the end of fertile-type mucus, 3 consecutive days of urinary PDG above 5 µg/mL is 100% specific to confirm ovulation. This data demonstrates a potential future use of a PDG urinary assay. The remarkable specificity of a PDG assay could enable women to accurately identify the infertile period following ovulation, and thus help them avoid pregnancy more effectively.
“After the first positive urinary LH test or the end of fertile-type mucus, 3 consecutive days of urinary PDG above 5 µg/mL is 100% specific to confirm ovulation.”
There are several notable limitations to this study. Although the measurement of PDG provides a promising means to identify the post-ovulation infertile phase, it cannot be applied to the pre-ovulatory infertile window. Furthermore, the study did not include women with any gynecologic pathologies, surgeries, or anomalies. Future studies must be done to determine the specificity in a group more representative of the greater population.
In summary, this study demonstrated that the use of urinary PDG measurements can confirm ovulation has occurred with accuracy, which is useful information to help couples identify the end of their fertile window. Since the Marquette Model employs a urinary hormone monitor that identifies the start of the fertile window, perhaps these assessments could be used in conjunction to help couples successfully identify the opening and closing of their fertile window through the use of urinary hormone monitoring alone. Additional studies would need to be done to assess the effectiveness of this approach to prevent pregnancy.
 Ecochard R, Leiva R, Bouchard T, Boehringer H, Direito A, Mariani A, Fehring R. Use of urinary pregnanediol 3- glucuronide to confirm ovulation. Steroids. 2013 Oct;78(10):1035-40. doi: 10.1016/j.steroids.2013.06.006. Epub 2013 Jul 4. PMID: 23831784.
ABOUT THE AUTHOR
Julianne Hall, MD
Julianne Hall, MD is a recent graduate of Georgetown University School of Medicine in Washington, DC. She completed her undergraduate education at Pennsylvania State University. She plans to pursue residency in emergency medicine and is interested in global health and wilderness medicine. Dr. Hall hopes to provide care to communities in remote, austere environments throughout her career. She participated in the FACTS elective as a fourth-year medical student to gain a better understanding of women’s reproductive health and cycles. She believes it is her duty to help her community and future patients feel more empowered over their health and reproductive decisions.