Ecochard R et al., 2024·Human reproduction (Oxford, England)
What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. Oestrogen enhances cervical mucus secretion while progesterone inhibits it. STUDY DESIGN, SIZE, Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. PARTICIPANTS/MATERIALS, SETTING, Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva. MAIN Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle. LIMITATIONS, This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings. This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflicts of interest. No funding was provided for this secondary data analysis. N/A.
Abdullah S et al., 2023·Hormone molecular biology and clinical investigation
During normal menstrual cycles, serum levels of progesterone vary widely between cycles of same woman and between women. This study investigated the profiles of pregnanediol during the luteal phase. Data stemmed from a previous multicenter prospective observational study and concerned 107 women (who contributed 326 menstrual cycles). The study analyzed changes in observed cervical mucus discharge, various hormones in first morning urine, and serum progesterone. Transvaginal ultrasonography and cervical mucus helped identifying the day of ovulation. Changes in pregnanediol glucuronide levels during the luteal phase were examined and classified according to the length of that phase, a location parameter, and a scale parameter. Associations between nine pregnanediol glucuronide profiles and other hormone profiles were examined. Low periovulatory pregnanediol glucuronide levels and low periovulatory luteinizing hormone levels were associated with delayed increases in pregnanediol glucuronide after ovulation. That 'delayed increase profile' was more frequently associated with cycles with prolonged high LH levels than in cycles with rapid pregnanediol glucuronide increases. A 'plateau-like profile' during the luteal phase was associated with longer cycles, cycles with higher estrone-3-glucuronide and pregnanediol glucuronide during the preovulatory phase, and cycles with higher periovulatory pregnanediol glucuronide levels. Distinct profiles of urinary progesterone levels are displayed during the luteal phase. These profiles relate to early hormone changes during the menstrual cycle. In everyday clinical practice, these findings provide further evidence for recommending progesterone test seven days after the mucus peak day. The search for other correlations and associations is underway.
Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle. Observational study. Study carried out from 1996 to 1997 in eight European family planning clinics. PARTICIPANT(S): One hundred and seven normally fertile and cycling women. MAIN OUTCOME MEASURE(S): BBT and PDG level on each day of 283 cycles and ultrasound determination of the day of ovulation. (s): In comparison with previous end-of-cycle levels, decreases in PDG and BBT on the first day of menses were seen in nearly 90% and 80% of cycles, respectively. In a non-negligible percentage of cycles, luteolysis would continue during menses: between the second and the third day after menses, small but significant decreases in PDG and BBT were seen in 76% and 48% of cycles, respectively. During the peri-ovulatory phase, between the third and the second day before ovulation, PDG and BBT began to rise in 56% and 41% of cycles, respectively. There was a medium degree of correlation between PDG levels and BBT (r = 0.53; 7,279 days with available measurements). The relationship between PDG levels and BBT was linear at low PDG levels but BBT increased no longer when PDG levels continued to rise above a threshold of nearly 10 mcg/mg Cr. (s): PDG and BBT had parallel increases at low PDG rates but diverged at higher rates.
To characterize the variability of hormonal profiles during the luteal phase in normal cycles. Observational study. Not applicable. PATIENT(S): Ninety-nine women contributing 266 menstrual cycles. INTERVENTION(S): The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation. MAIN OUTCOME MEASURE(S): The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10 μg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10 μg/mg Cr. RESULT(S): Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle. CONCLUSION(S): The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis.
Serum progesterone (P) rises after ovulation in the luteinisation process. To identify an accurate progesterone threshold to confirm ovulation in the assessment of a woman's fertility. In a secondary analysis of an observational European multicentre study, this study included 107 women over 326 menstrual cycles and tracked daily first morning urine (FMU), changes in observed cervical mucus discharge, serum progesterone, and ultrasonography to identify the day of ovulation. A serum progesterone level was available for 102 women over a total 260 cycles with one or two P levels per cycle. It was found that a single serum P⩾5ng/ml is highly specific with a specificity of 98.4 (95% CI 96.0-99.5), with a sensitivity of 89.6 (95% CI 85.2-92.9). A random serum progesterone level ⩾5ng/ml confirms ovulation. This may be of use for clinicians wanting to confirm that ovulation has occurred.
To describe FSH profile variants. Observational study. Multicenter collaborative study. PATIENT(S): A total of 107 women. INTERVENTION(S): Women collected daily first morning urine and underwent serial ovarian ultrasound. MAIN OUTCOME MEASURE(S) FSH RESULT(S): The individual FSH cyclic profiles demonstrated a significant departure from the currently accepted model. A decline in FSH levels at the end of the follicular phase was observed in only 42% of cycles. The absence of this decline was significantly associated with a shorter luteal phase and higher pregnanediol-3α-glucuronide, FSH, and LH levels at the time of ovulation. In 34% of the cycles, significant FSH variability was observed throughout the follicular phase; this variability was associated with higher body mass index and lower overall FSH and LH levels throughout the cycle. The FSH peak occurs on average 2 hours before ovulation. The FSH peak duration was shorter than the LH peak. CONCLUSION(S): These results suggest that average FSH profiles may not reflect the more complex dynamics of daily hormonal variations in the menstrual cycle. It is possible that discrepancies between the average normal FSH profile and the individual day-to-day variants can be used to detect abnormalities.
Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine.
To monitor gonadotropin and ovarian hormone levels in relation to sleep duration in normally cycling women. Observational and cross-sectional study. Multicentric collaborative study. PATIENT(S): One hundred six healthy and normally cycling women, aged 19 to 44 years, with cycle lengths of 24 to 34 days. INTERVENTION(S): Follow-up during one to four consecutive cycles with daily urine collection. MAIN OUTCOME MEASURE(S): Urine concentrations of LH, FSH, estrone-3-glucuronide (E1-3-G), and pregnanediol-3-alpha-glucuronide (Pd-3alpha-G). Ultrasound determination of day of ovulation and estimation of sleep duration. RESULT(S): We found a significant association between FSH levels and sleep duration (P=.008). Follicle-stimulating hormone levels were 20% higher in long-time sleepers than in short-time sleepers. This association persisted whatever the age or the body mass index. There was no significant association between belonging to any group and LH, E1-3-G, or Pd-3alpha-G levels. CONCLUSION(S): Our results suggest that sleep duration could be related to FSH levels, although the study design did not allow us to establish a causal relationship nor to explain the physiological basis of the observed relationship.
To improve prediction of ovulation in normal cycles. Collection of women's characteristics and their menstrual cycles. Monitoring and analysis of time relationships between several indicators of ovulation: transvaginal ultrasonography, cervical mucus, basal body temperature, urinary luteinising hormone, and ratio of urinary oestrogen to progesterone metabolites. Each of eight natural family planning clinics was to study 12 women for at least three cycles. One hundred and seven normally fertile and cycling women aged 18 to 45. Daily measurements of urinary luteinising hormone, follicle stimulating hormone, oestrone-3-glucuronide and pregnanediol-3alpha-glucuronide. Basal body temperature recording and cervical mucus checking. Transvaginal ultrasound examination of the ovaries. Delays between the expected day of ovulation according to the luteinising hormone peak or to ultrasound evidence and the expected days according to the other indices of ovulation. Ultrasonography was able to show evidence of ovulation in 283 out of 326 cycles. The average time lag between luteinising hormone peak and ultrasound evidence was less than one day (+0.46) but premature and late luteinising hormone-expected date of ovulation were observed in nearly 10% and 23% of cycles, respectively. Basal body temperature rise was observed in 98% of cycles. Cervical mucus peak symptom, rapid drop in the ratio of urinary metabolites, and luteinising hormone initial rise were all close to ultrasonographic evidence in more than 72% of cycles. For accuracy and practical reasons, the cervical mucus peak symptom, the ratio of urinary metabolites and luteinising hormone initial rise might be better indices of ovulation than the luteinising hormone peak.
Ecochard R et al., 2001·European journal of obstetrics, gynecology, and reproductive biology
Women with cyclic mastalgia seem to be at risk of fibrocystic breast disease and/or breast cancer. We studied the relationships between mastalgia and hormone levels throughout the menstrual cycle. Ostensibly healthy women were monitored during a sum of 326 cycles. A case-control study compared personal and hormonal variables of 30 women experiencing cyclic mastalgia with those of 77 women without this symptom. Except sleeping times, no significant differences were found in personal variables. Cyclic mastalgia and symptoms of fluid retention were slightly associated. Menses and the luteal phase were significantly longer in cases than in controls. Gonadotropin but not ovarian hormone levels were also significantly higher in cases throughout the cycle. Cyclic mastalgia is less related to symptoms of fluid retention or to ovarian hormone levels than to regularly high gonadotropin levels, specific inhibitors might thus be used to alleviate the symptom.
Ecochard R et al., 2000·European journal of obstetrics, gynecology, and reproductive biology
Evaluation of sensitivity and specificity of 4 ultrasound indices of ovulation. Multicenter collaborative study of 794 abdominal and transvaginal ultrasound scanning of ovaries performed during 271 cycles in 107 normally fertile women. Comparison of sensitivities and specificities of indices using McNemar test. The sensitivity and specificity of the indices were 84 and 89.2, respectively, for disappearance or sudden decrease in follicle size; 38.4 and 79.7 for appearance of ultrasonic echoes in the follicle; 61.6 and 87.1 for irregularity of follicular walls; 71.0 and 88.2 for appearance of free fluid in the cul-de-sac of Douglas. Ultrasonic echoes had a significantly lower sensitivity (P<0.001) and specificity (P<0.01) than other indices.
To characterize the relationships between body mass index (BMI) and LH or FSH levels over the cycle in normally cycling women. We compared baseline characteristics, cycle characteristics, follicle sizes, and daily hormone levels among women with low (n = 22), normal (n = 63), or high (n = 22) BMIs over 326 cycles. There were no significant differences in age or other lifestyle characteristics between groups. High BMI was significantly associated with younger age at menarche and less sleeping time. No differences were observed between high- and low-BMI groups in cycle length or diameter of the dominant follicle. Luteinizing hormone levels were significantly higher only in the beginning of the cycle in women with low BMIs than in those with high BMIs. Follicle-stimulating hormone levels were also significantly higher but were high during all three phases of the cycle (early follicular, periovulatory, and luteal phases). Mean levels were approximately 1. 9, 1.8, and 1.2 times higher, respectively, in the low-BMI group than the high-BMI group. Luteinizing hormone levels and BMI were inversely associated in normally cycling women during the early follicular phase. Follicule-stimulating hormone levels and BMI were inversely associated during the whole cycle, independent of age.