The menstrual cycle is influenced by weekly and lunar rhythms.

OBJECTIVE: To study whether the menstrual cycle has a circaseptan (7 days) rhythm and whether it is associated with the lunar cycle (also defined as the synodic month, it is the cycle of the phases of the Moon as seen from Earth, averaging 29.5 days in length). DESIGN: Cross-sectional study. SUBJECTS: A total of 35,940 European and North American women aged 18-40 years. EXPOSURE: Data were collected in real-life conditions. INTERVENTION: No intervention was performed. MAIN OUTCOME MEASURE: The onset of menstruation was assessed in prospectively measured menstrual cycles (311,064 cycles) over 3 full years (2019-2021). Associations were calculated between the onset of menstruation and the day of the week, and between the onset of menstruation and the lunar phase. RESULTS: In this large data set, a circaseptan (7-day) rhythmicity of menstruation was observed, with a peak (acrophase) of menstrual onset on Thursdays and Fridays. This circaseptan rhythm was observed in every age group, in every phase of the lunar cycle, and in all seasons. This feature was most pronounced for cycle durations between 27 and 29 days. In winter, the circaseptan rhythm was found in cycles of 27-29 days, but not in other cycle lengths. A circalunar rhythm was also statistically significant, but not as clearly defined as the circaseptan rhythm. The peak (acrophase) of the circalunar rhythm of menstrual onset varied according to the season. In addition, there was a small but statistically significant interaction between the circaseptan rhythm and the lunar cycle. CONCLUSION: Although relatively small in amplitude, the weekly rhythm of menstruation was statistically significant. Menstruation occurs more often on Thursdays and Fridays than on other days of the week. This is particularly true for women whose cycles last between 27 and 29 days. Circalunar rhythmicity was also statistically significant. However, it is less pronounced than the weekly rhythm.

Using Quantitative Hormone Monitoring to Identify the Postpartum Return of Fertility.

Background and Objectives: The Marquette Method (MM) has been used for many years to track the postpartum return of fertility using the ClearBlue Fertility Monitor (CBFM). A new quantitative urine hormone monitor (the Mira Analyzer) was compared to the CBFM in one previous study, and using this pilot data, several women have started to use the Mira Analyzer in the postpartum transition to fertility. Materials and Methods: This study was a retrospective, observational case series that analyzed hormone data on the Mira Analyzer during the postpartum period. Participants were invited to share their postpartum cycle and hormone observations. Quantitative hormones in the urine included estrone-3-glucuronide (E3G), luteinizing hormone (LH), and pregnanediol glucuronide (PDG). Data were collected using an electronic survey and an online portal for hormone data. Data collected included participant demographics, menstrual cycle characteristics, and reproductive health history. Hormone range values were calculated, and thresholds were identified that would best predict the first ovulation that led to the first postpartum menstrual period, as well as in transition cycles. Hormone patterns were identified in the context of previous studies. Results: Twenty participants contributed data for the analysis. Triggering ovulation before the first period postpartum (Cycle 0) usually required higher LH thresholds than for regularly cycling women. Three different patterns were observed in the return of fertility postpartum: minimal ovarian activity, follicular activity without ovulation, and the early return of fertility. Abstinence rates for avoiding pregnancy with experimental thresholds were calculated. Conclusions: Higher LH thresholds in Cycle 0 suggest a decreased responsiveness of the ovaries to LH stimulation from the pituitary. This study replicates postpartum hormone patterns from a previous study. Larger studies are planned to evaluate the effectiveness for avoiding pregnancy using the Mira Analyzer in the postpartum return of fertility.

Survey Analysis of Quantitative and Qualitative Menstrual Cycle Tracking Technologies.

Background and Objectives: Digital health and personalized medicine are advancing at an unprecedented pace. Users can document their menstrual cycle data in a variety of ways, including smartphone applications (apps), temperature tracking devices, and at-home urine hormone tests. Understanding the needs and goals of women using menstrual cycle tracking technologies is the first step to making these technologies more evidence based. The purpose of this study was to examine the current use of these technologies and explore how they are being used within the context of common hormonal and reproductive disorders, like polycystic ovary syndrome (PCOS), endometriosis, and infertility. Materials and Methods: This was a cross-sectional study evaluating menstrual cycle tracking technology use. Participants were recruited in January-March 2023 using social media groups and a Marquette Method instructor email listserv. Data were collected using an electronic survey with Qualtrics. Data collected included participant demographics, menstrual cycle characteristics, reproductive health history, and menstrual cycle tracking behavior. Results: Three-hundred and sixty-eight participants were included in the analysis. Women had various motivations for tracking their menstrual cycles. Most participants (72.8%) selected "to avoid getting pregnant" as the primary motivation. Three hundred and fifty-six participants (96.7%) reported using a fertility awareness-based method to track and interpret their menstrual cycle data. The Marquette Method, which utilizes urine hormone tracking, was the most frequently used method (n = 274, 68.2%). The most frequently used cycle technology was a urine hormone test or monitor (n = 299, 81.3%), followed by a smartphone app (n = 253, 68.8%), and a temperature tracking device (n = 116, 31.5%). Women with PCOS (63.6%), endometriosis (61.8%), and infertility (75%) in our study reported that the use of tracking technologies aided in the diagnosis. Most participants (87.2%) reported a high degree of satisfaction with their use and that they contributed to their reproductive health knowledge (73.9%). Conclusions: Women in our study reported avoiding pregnancy as their primary motivation for using menstrual cycle tracking technologies, with the most frequently used being a urine hormone test or monitor. Our study results emphasize the need to validate these technologies to support their use for family planning. Given that most women in this study reported using a fertility awareness-based method, the results cannot be generalized to all users of menstrual cycle tracking technologies.

Using Quantitative Hormonal Fertility Monitors to Evaluate the Luteal Phase: Proof of Concept Case Study.

Several new quantitative fertility monitors are now available for at-home use that measure estrogen, luteinizing hormone (LH), and progesterone (PDG) in urine. This case report compares the Mira and Inito quantitative fertility monitors with the well-established qualitative ClearBlue fertility monitor. Three clinical scenarios were evaluated: a normal cycle, a prolonged luteinization cycle, and an anovulatory cycle. The identification of the luteal phase (or lack thereof in the case of anovulation) and the transition through the three processes of luteinization, progestation, and luteolysis were clearly demarcated with the help of quantitative LH and PDG. Quantitative fertility monitors have the potential to identify details of the luteal phase to help women with regular cycles and abnormal luteal phases to help target interventions for optimizing fertility.

Menstrual Cycle Parameters Are Not Significantly Different After COVID-19 Vaccination.

Background: Some studies have suggested minor changes in the menstrual cycle after COVID-19 vaccination, but more detailed analyses of the menstrual cycle are needed to evaluate more specific changes in the menstrual cycle that are not affected by survey-based recall bias. Materials and Methods: Using a pretest-post-test quasi-experimental evaluation of menstrual cycle parameters before and after COVID-19 vaccination, we conducted an anonymous online survey of two groups of North American women who prospectively monitor their menstrual cycle parameters daily including bleeding patterns, urinary hormone levels using the ClearBlue Fertility Monitor, or cervical mucus observations. The primary outcome measures were cycle length, length of menses, menstrual volume, estimated day of ovulation (EDO), luteal phase length, and signs of ovulation. Perceived (subjective) menstrual cycle changes and stressors were also evaluated in this study as secondary outcome measures. Results: Of the 279 women who initiated the survey, 76 met the inclusion criteria and provided 588 cycles for analysis (227 pre-vaccine cycles, 145 vaccine cycles, 216 post-vaccine cycles). Although 22% of women subjectively identified changes in their menstrual cycle, there were no significant differences in menstrual cycle parameters (cycle length, length of menses, EOD, and luteal phase length) between the pre-vaccine, vaccine, and post-vaccine cycles. Conclusions: COVID-19 vaccines were not associated with significant changes in menstrual cycle parameters. Perceived changes by an individual woman must be compared with statistical changes to avoid confirmation bias.

Quantitative versus qualitative estrogen and luteinizing hormone testing for personal fertility monitoring.

BACKGROUND: A new fertility monitor is now available that provides quantitative measurement of urinary hormones, but clinical use requires validation against an established fertility monitor that provides only qualitative results. RESEARCH DESIGN AND METHODS: Two fertility monitors were compared using daily first morning urine samples over 3 cycles of use in 21 women users with experience using a fertility monitor with the Marquette Method of Natural Family Planning. RESULTS: Women were aged 33.4 ± 5.5 years and had menstrual cycles ranging between 23 and 41 days. The quantitative Mira Monitor estimates of ovulation were highly correlated with the qualitative ClearBlue Fertility Monitor (CBFM) estimates of ovulation. Both monitors provided an accurate estimate of the fertile window. CONCLUSIONS: In this preliminary trial, the Mira monitor was shown to be effective at delineating the fertile window and ovulation. We demonstrated the feasibility of applying the Marquette Method algorithm with the use of the Mira monitor. Satisfaction differences between the two monitors did not reach statistical significance. We anticipate that quantitative fertility monitoring will give couples and health-care providers new and unprecedented insights into the menstrual cycle and fertility.

Pilot Evaluation of a New Urine Progesterone Test to Confirm Ovulation in Women Using a Fertility Monitor.

Background: Progesterone rises ~24-36 h after ovulation. Past studies using ultrasound-confirmed ovulation have shown that three consecutive tests with a threshold of 5µg/mL of urine progesterone (pregnanediol-3-glucuronide, PDG), taken after the luteinizing hormone (LH) surge, confirmed ovulation with 100% specificity. Purpose: The purpose of this study was to a evaluate a new urine PDG self-test to retrospectively confirm ovulation in women who were monitoring ovulation using a hormonal fertility monitor. Methods: Thirteen women of reproductive age were recruited to test urine PDG while using their home hormonal fertility monitor. The monitor measured the rise in estrogen (estrone-3-glucuronide, E3G) and LH to estimate the fertile phase of the menstrual cycle. The women used an online menstrual cycle charting system to track E3G, LH and PDG levels for four menstrual cycles. Results: The participants (Mean age 33.6) produced 34 menstrual cycles of data (Mean length 28.4 days), 17 of which used a PDG test with a threshold of 7µg/mL and 17 with a threshold of 5µg/mL. In the cycles that used the 7µg/mL test strips, 59% had a positive confirmation of ovulation, and with the 5µg/mL test strips, 82% of them had a positive confirmation of ovulation. Conclusion: The 5µg/mL PDG test confirmed ovulation in 82% of cycles and could assist women in the evaluation of the luteal progesterone rise of their menstrual cycle.

Hormonal Predictors of Abnormal Luteal Phases in Normally Cycling Women.

Objective: Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women. Design: Observational study. Setting: Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3- alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four outcome measures were analyzed: short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level. Results: A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG. Conclusion: Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.

Achieving Pregnancy Using Primary Care Interventions to Identify the Fertile Window.

OBJECTIVE: To determine the effectiveness of achieving pregnancy with focused intercourse in the fertile window identified using natural fertility indicators. METHODS: 24-cycle prospective effectiveness study. SETTING: A North American web-based fertility monitoring service. PARTICIPANTS: 256 North American women aged 20-43 (mean age 29.2 years) seeking to achieve pregnancy. INTERVENTION: Participants identified their fertile window with either electronic hormonal fertility monitoring or cervical mucus monitoring, or both, and recorded their observations on an online fertility tracking system. MAIN OUTCOME MEASURES: Pregnancies were validated by nurses with an online self-assessed pregnancy evaluation form. Survival analysis was used to determine pregnancy rates. RESULTS: There were 150 pregnancies among the 256 participants with an overall pregnancy rate of 78 per 100 women over 12 menstrual cycles. There were 54 pregnancies (68%) among the 80 women using the fertility monitor, 11 pregnancies (46%) among the 24 women using mucus monitoring, and 90 (63%) among the 143 women using both mucus and monitor. The 12-cycle pregnancy rates per 100 women were 83 (monitor group), 72 (mucus group), and 75 (mucus and monitor group). Pregnancy rates reached 100% at 24 cycles of use for those women using the hormonal fertility monitor. CONCLUSION: Use of the hormonal fertility monitor alone seems to offer the best natural estimate of the fertile phase of the menstrual cycle for women wishing to achieve a pregnancy. Focusing intercourse through 24 menstrual cycles can be beneficial for achieving pregnancy.

Combination of Micronutrients for Bone (COMB) Study: bone density after micronutrient intervention.

Along with other investigations, patients presenting to an environmental health clinic with various chronic conditions were assessed for bone health status. Individuals with compromised bone strength were educated about skeletal health issues and provided with therapeutic options for potential amelioration of their bone health. Patients who declined pharmacotherapy or who previously experienced failure of drug treatment were offered other options including supplemental micronutrients identified in the medical literature as sometimes having a positive impact on bone mineral density (BMD). After 12 months of consecutive supplemental micronutrient therapy with a combination that included vitamin D(3), vitamin K(2), strontium, magnesium and docosahexaenoic acid (DHA), repeat bone densitometry was performed. The results were analyzed in a group of compliant patients and demonstrate improved BMD in patients classified with normal, osteopenic and osteoporotic bone density. According to the results, this combined micronutrient supplementation regimen appears to be at least as effective as bisphosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micronutrient protocol. This micronutrient regimen also appears to show efficacy in individuals where bisphosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy.

High-tech family planning: reproductive regulation through computerized fertility monitoring.

Issues related to family planning have profound public health significance as they directly impact individuals, couples, and families throughout the world. A new method of family planning is now available using a computerized fertility monitor that accurately measures urinary surges in estrone-3-glucuronide (E3G) and luteinizing hormone (LH) prior to ovulation, thus identifying the short-lived fertile phase of the cycle and providing women with the choice to achieve or avoid conception. As well as ease of use and instruction, hand-held computerized fertility monitors are accurate and effective and can be used indefinitely. An algorithm for computerized monitoring is presented for use in situations of infrequent or irregular ovulation such as with polycystic ovarian syndrome and the post-partum period. Hormone-based fertility monitoring is compared to other computerized fertility monitoring techniques. A case series of seven reports reflecting varied clinical backgrounds and medical histories demonstrates broad-based success and high satisfaction with computerized monitoring for regulation of reproductive potential. Limitations of fertility monitoring are also discussed.

Celiac disease presenting as autism.

Gluten-restricted diets have become increasingly popular among parents seeking treatment for children diagnosed with autism. Some of the reported response to celiac diets in children with autism may be related to amelioration of nutritional deficiency resulting from undiagnosed gluten sensitivity and consequent malabsorption. A case is presented of a 5-year-old boy diagnosed with severe autism at a specialty clinic for autistic spectrum disorders. After initial investigation suggested underlying celiac disease and varied nutrient deficiencies, a gluten-free diet was instituted along with dietary and supplemental measures to secure nutritional sufficiency. The patient's gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of autism progressively abated. This case is an example of a common malabsorption syndrome associated with central nervous system dysfunction and suggests that in some contexts, nutritional deficiency may be a determinant of developmental delay. It is recommended that all children with neurodevelopmental problems be assessed for nutritional deficiency and malabsorption syndromes.

Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism.

OBJECTIVES: To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients. DESIGN: Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method. RESULTS: Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum. CONCLUSIONS: Cortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients.

Homocysteine is not associated with global motor or cognitive measures in nondemented older Parkinson's disease patients.

Levodopa (L-dopa) treatment of Parkinson's disease (PD) is associated with elevated homocysteine (Hcy). To examine the relationship between Hcy, methylenetetrahydrofolate reductase polymorphisms (MTHFR: 677C/T; 1298A/C), and B-vitamins in older PD patients and whether Hcy or MTHFR polymorphisms were associated with clinical measures. MTHFR polymorphisms, B-vitamin intake, and blood concentrations of Hcy, vitamin B12 and folate, and creatinine were determined and compared between groups (PD and controls). The relationship of Hcy to clinical measures was examined in PD. Among 51 patients [30M/21F, mean age (SD): 71.5 (4.7)] and 50 controls [29M/21F, 71.5 (4.8)], Hcy was higher in PD [13.6 (3.8); controls: 10.5 (2.5), P < 0.0005]. Hcy was associated with B-vitamin intake [F = 21.7, P < 0.0005], folate level (R = 0.31, P = 0.035), and the interaction of intake with MTHFR 677T (F = 5.2, P = 0.007), but not MTHFR 1298C genotype. Hcy did not correlate with global measures of cognition, mood, or parkinsonism in PD or with dyskinesias, fluctuations, or freezing. Higher vitamin B12 levels were associated with lower dyskinesia risk. Hcy was influenced by PD, MTHFR 677 genotype, and vitamin use, but not by the MTHFR 1298 genotype. There was no clear association with motor or cognitive measures, but dyskinesias were less likely with higher B12.

Aging hippocampus and amygdala.

Earlier studies suggest that the anterior hippocampus may show resilience to age-associated volume loss. This study compared high-resolution magnetic resonance images obtained from younger (n=28; age range: 22-50 years) and older (n=39; age range: 65-84 years) healthy right-handed individuals to determine whether age-related volume changes varied between the hippocampal head, body and tail. Volumetric reductions were progressively more severe from hippocampal head to tail. Amygdala volume differences were intermediate in size. Although limited by the cross-sectional design, these data suggest that hippocampal subregions show a gradient of volume reduction in healthy aging that contrasts with the preferential reduction of anterior hippocampal volumes in Alzheimer's and Parkinson's diseases.

Age and dementia-associated atrophy predominates in the hippocampal head and amygdala in Parkinson's disease.

The hippocampus (HC) and amygdala (AG) decrease in volume with age and in Parkinson's disease (PD) with (PDD) and without dementia. We compared 44 PD to 44 age, sex and education-matched subjects without PD (non-PD) and 13 PDD subjects. T1-weighted MR images were used to manually segment the head, body and tail of the HC and the AG. HC volumes, corrected to intracranial volume, were smaller in PDD than non-PD (p=0.04), reflected predominantly by head atrophy. Right AG volumes were smaller in PD compared to non-PD (p=0.03). HC volumes in older (>70), but not younger, non-demented PD differed from non-PD (HC, p=0.02; head, p=0.03). Age correlated negatively with overall HC (r=-0.43, p=0.004) and head (r=-0.48, p=0.001) in PD, but not in non-PD. In PD, left HC head volumes correlated with recall, but not recognition scores on the CVLT-II (r=0.35, p=0.02) and BVMT-R (r=0.35, p=0.02); AG volumes correlated with CVLT-II recall (r=0.35, p=0.02). No correlations were found in non-PD (p>0.4). In conclusion, functionally meaningful age-associated hippocampal and amygdala atrophy occurs in PD.

Three-dimensional volumetric analysis and reconstruction of amygdala and hippocampal head, body and tail.

Volumetric changes in the amygdala and hippocampus are relevant to many disorders, but their close proximity makes it difficult to separate these structures by magnetic resonance imaging, leading many volumetric protocols to exclude problematic slices from analysis, or to analyze the amygdalo-hippocampal complex conjointly. The hippocampus tail is also often excluded, because of the difficulty in separating it from the thalamus. We have developed a reliable protocol for volumetric analysis and 3-D reconstruction of the amygdala and hippocampus (as a whole and in its anatomical parts). Twenty volunteers from clinical and healthy populations were recruited. T1-weighted images were acquired at 1.5 Tesla with native spatial resolution of 1.5 mm x 1.0 mm x 1.0 mm. Volumetric analyses were performed blind to diagnosis, using the interactive software package DISPLAY. Inter-rater (intrarater) intraclass correlations for the method were: 0.95 (0.88) for hippocampus tail, 0.83 (0.93) for hippocampus body, 0.95 (0.92) for hippocampus head, 0.96 (0.86) for total hippocampus and 0.86 (0.94) for amygdala. Volumes (mean+/-S.D.) corrected for intracranial volume for this mixed group were for the hippocampal tail: 0.325+/-0.087 cm(3); hippocampal body: 0.662+/-0.120 cm(3); hippocampal head: 1.23+/-0.174 cm(3); total hippocampus: 2.218+/-0.217 cm(3), and amygdala: 0.808+/-0.185 cm(3). In conclusion, the study demonstrates that the amygdala and hippocampal parts can be quantified reliably.