Distinct urinary progesterone metabolite profiles during the luteal phase.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Descriptive analysis of the relationship between progesterone and basal body temperature across the menstrual cycle.

OBJECTIVE: Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle. DESIGN: Observational study. SETTING: 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. RESULT: (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. CONCLUSION: (s): PDG and BBT had parallel increases at low PDG rates but diverged at higher rates.

Lateral Flow Assays in Infectious Disease Diagnosis.

BACKGROUND: Lateral flow immunoassays are widely used as diagnostic tests in many applications in human and other diagnostic areas. Assays for human applications have been commercially available since the 1980s and initially were primarily used to identify pregnancy by measuring human chorionic gonadotropin in urine and serum/plasma. CONTENT: The first infectious disease lateral flow assays were commercialized in the late 1980s identifying the presence of Group A Streptococcus pyogenes collected with throat swabs; innumerable other applications followed in the intervening decades. The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic has brought a vast number of new assays for which emergency use authorization (EUA) has been requested in the USA. These assays have been designed for detection of the antibody response to an infection and viral antigens in respiratory samples. In view of the onslaught of new tests, this review will focus on the use of rapid lateral flow immunoassays for infectious diseases. Principles of lateral flow assays and approaches to the production of high-sensitivity point-of-care assays are presented. Market trends, customer requirements, and future directions of lateral flow assay technology and its applications in the infectious disease diagnostic space are discussed. SUMMARY: Lateral flow immunoassays play an important role in infectious disease diagnostics. Advancements in technology have led to improved performance of these assays and acceptance by professional users. With the advent of the SARS-CoV-2 pandemic, the market has reached new levels requiring hundreds of millions of tests per year for professional and even home use.

A first of its kind quantitative functional C1-esterase inhibitor lateral flow assay for hereditary angioedema point-of-care diagnostic testing.

Hereditary Angioedema (HAE) is a rare, autosomal dominant disease caused by mutations in SERPING1 gene leading to dysfunction/deficiency of C1-esterase inhibitor (C1-INH) protein and subsequent dysregulation of the contact system and bradykinin overproduction. As functional C1-INH (fC1-INH) levels are reduced in HAE types I and II (HAE-I/II), a specific, sensitive and accessible rapid diagnostic method to quantitate fC1-INH is crucial in diagnosing HAE-I/II. Previously, we developed/validated methods to detect fC1-INH levels in human plasma based on functional binding to C1s or FXIIa for C1-INH-based therapies. Quantitative fC1-INH immunoassay methods were converted to the Lateral flow assay (LFA) platform after identifying the best reagent/s pair. The assay was developed and optimized as a first of its kind LFA method for quantifying fC1-INH in human plasma to aid HAE point-of-care diagnosis. Receiver operating characteristic analysis was performed using normal control and HAE subject plasma samples to calculate area-under-curve and a cut-off point to distinguish normal versus HAE subject samples. LFA data was correlated with the conventional diagnostic assay for fC1-INH in HAE plasma samples and profiles matched for individual subjects. Here, we demonstrate a proof-of-concept for the quantitative fC1-INH LFA using normal and HAE plasma samples. We propose that the method could be used as a point-of-care test to diagnose HAE in a variety of settings, such as, a hospital or physician's office, at home or in an ambulance.

Characterization of hormonal profiles during the luteal phase in regularly menstruating women.

OBJECTIVE: To characterize the variability of hormonal profiles during the luteal phase in normal cycles. DESIGN: Observational study. SETTING: 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.

Characterization of follicle stimulating hormone profiles in normal ovulating women.

OBJECTIVE: To describe FSH profile variants. DESIGN: Observational study. SETTING: 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.

Relationship between sleep and secretion of gonadotropin and ovarian hormones in women with normal cycles.

OBJECTIVE: To monitor gonadotropin and ovarian hormone levels in relation to sleep duration in normally cycling women. DESIGN: Observational and cross-sectional study. SETTING: 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.