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      A Validated Normative Model for Human Uterine Volume from Birth to Age 40 Years

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          Abstract

          Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non-invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone. The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume.

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          A Validated Model of Serum Anti-Müllerian Hormone from Conception to Menopause

          Thomas Kelsey, Phoebe Wright, Scott M. Nelson … (2011)
          Background Anti-Müllerian hormone (AMH) is a product of growing ovarian follicles. The concentration of AMH in blood may also reflect the non-growing follicle (NGF) population, i.e. the ovarian reserve, and be of value in predicting reproductive lifespan. A full description of AMH production up to the menopause has not been previously reported. Methodology/Principal Findings By searching the published literature for AMH concentrations in healthy pre-menopausal females, and using our own data (combined ) we have generated and robustly validated the first model of AMH concentration from conception to menopause. This model shows that 34% of the variation in AMH is due to age alone. We have shown that AMH peaks at age 24.5 years, followed by a decline to the menopause. We have also shown that there is a neonatal peak and a potential pre-pubertal peak. Our model allows us to generate normative data at all ages. Conclusions/Significance These data highlight key inflection points in ovarian follicle dynamics. This first validated model of circulating AMH in healthy females describes a transition period in early adulthood, after which AMH reflects the progressive loss of the NGF pool. The existence of a neonatal increase in gonadal activity is confirmed for females. An improved understanding of the relationship between circulating AMH and age will lead to more accurate assessment of ovarian reserve for the individual woman.
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            Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network.

            Gary G. Koch, C Hasemeier, E J Slora … (1997)
            To determine the current prevalence and mean ages of onset of pubertal characteristics in young girls seen in pediatric practices in the United States. A cross-sectional study was conducted by 225 clinicians in pediatric practices belonging to Pediatric Research in Office Settings, a practice-based research network. After standardized training in the assessment of pubertal maturation, practitioners rated the level of sexual maturation on girls 3 through 12 years who were undergoing complete physical examinations. Data were analyzed for 17,077 girls, of whom 9.6% were African-American and 90.4% white. At age 3, 3% of African-American girls and 1% of white girls showed breast and/or pubic hair development, with proportions increasing to 27.2% and 6.7%, respectively, at 7 years of age. At age 8, 48.3% of African-American girls and 14.7% of white girls had begun development. At every age for each characteristic, African-American girls were more advanced than white girls. The mean ages of onset of breast development for African-American and white girls were 8.87 years (SD, 1.93) and 9.96 years (SD, 1.82), respectively; and for pubic hair development, 8.78 years (SD, 2.00) and 10.51 years (SD, 1.67), respectively. Menses occurred at 12.16 years (SD, 1.21) in African-American girls and 12.88 years (SD, 1.20) of age in white girls. These data suggest that girls seen in a sample of pediatric practices from across the United States are developing pubertal characteristics at younger ages than currently used norms. Practitioners may need to revise their criteria for referral of girls with precocious puberty, with attention to racial differences.
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              A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

              Thomas Kelsey, Lucy Q. Li, Rod T. Mitchell … (2014)
              The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5–97.5 percentile)] at 15.4 (7.2–31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5–97.5 percentile)] to 13.0 (6.6–25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.
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                Author and article information

                Contributors
                Cornelis B Lambalk: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 13 June 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 6
                Electronic Location Identifier: e0157375
                Affiliations
                [1 ]School of Computer Science, University of St Andrews, St Andrews KY16 9SX, United Kingdom
                [2 ]School of Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
                [3 ]Department of Paediatric Radiology, Royal Hospital for Sick Children, Edinburgh EH9 1LF, United Kingdom
                [4 ]Department of Endocrinology and Diabetes, Royal Hospital for Sick Children, Edinburgh EH9 1LF, United Kingdom
                [5 ]MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
                [6 ]Department of Haematology/Oncology, Royal Hospital for Sick Children, Edinburgh EH9 1LF, United Kingdom
                VU University Medical Center, NETHERLANDS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: TWK EG MMC WHBW. Performed the experiments: TWK EG MMC LEB WHBW. Analyzed the data: TWK EG RAA WHBW. Wrote the paper: TWK EG MMC LEB RAA WHBW.

                Author information
                http://orcid.org/0000-0002-8091-1458
                Article
                Publisher ID: PONE-D-16-06376
                DOI: 10.1371/journal.pone.0157375
                PMC ID: 4905658
                PubMed ID: 27295032
                SO-VID: 95850354-4aa7-48ed-8825-c6e35ce1b0d7
                Copyright © © 2016 Kelsey et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 14 February 2016
                Date accepted : 28 May 2016
                Page count
                Figures: 6, Tables: 5, Pages: 14
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Medicine and Health Sciences
                Subject: Radiology and Imaging
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Reproductive System
                Subject: Uterus
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Reproductive System
                Subject: Uterus
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Physiology
                Subject: Puberty
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Puberty
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Puberty
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Musculoskeletal System
                Subject: Pelvis
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Musculoskeletal System
                Subject: Pelvis
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Hormones
                Subject: Peptide Hormones
                Subject: Growth Hormone
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Reproductive System
                Subject: Genital Anatomy
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Reproductive System
                Subject: Genital Anatomy
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diagnostic Radiology
                Subject: Ultrasound Imaging
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Diagnostic Radiology
                Subject: Ultrasound Imaging
                Subject: Medicine and Health Sciences
                Subject: Radiology and Imaging
                Subject: Diagnostic Radiology
                Subject: Ultrasound Imaging
                Subject: Medicine and Health Sciences
                Subject: Health Care
                Subject: Health Services Research
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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