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Lauren R Cirrincione Department of Pharmacy, University of Washington, Seattle, Washington, USA

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Bridgit O Crews Department of Pathology and Laboratory Medicine, University of California Irvine, Orange, California, USA

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Jane A Dickerson Department of Laboratories, Seattle Children's Hospital, Seattle, Washington, USA

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Matthew D Krasowski Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

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Jessica Rongitsch Internal Medicine, Capitol Hill Medical, Seattle, Washington, USA

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Katherine L Imborek Department of Family Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

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Zil Goldstein Department of Medicine, Callen-Lorde Community Health Center, New York, New York, USA
CUNY Graduate School of Public Health and Health Policy, New York, New York, USA

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Dina N Greene Washington Kaiser Permanente, Renton, Washington, USA
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA

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time, and affordability ( 5 ). Despite these advantages, early reports established cross-reactivity between estrogenic metabolites (including unconjugated and conjugated estrone, a weak estrogen) and anti-estradiol antibodies used in immunoassays ( 4

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

risk for failure to attain peak bone mass or for early loss of BD, due to estrogen deficiency at an early age ( 1 , 2 , 3 , 4 , 5 ). Consequently, women with POI are advised to use hormone replacement therapy (HRT) ( 6 ). In contrast to POI, the

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Silvia Ciancia Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium

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Vanessa Dubois Basic and Translational Endocrinology (BaTE), Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Martine Cools Department of Internal Medicine and Pediatrics, Ghent University, Pediatric Endocrinology Service, Ghent University Hospital, Ghent, Belgium

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skeletal growth is not linear. Both androgens and estrogens contribute to bone size expansion and mineralization in both sexes, with the first process mainly driven by androgens and the second by estrogens ( 25 ). However, since in males, part of the

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Panagiotis Anagnostis Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Irene Lambrinoudaki 2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Medical School, Athens, Greece

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John C Stevenson National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

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Dimitrios G Goulis Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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–10 years later compared with males, mostly due to the protective effect of estrogens on the atherosclerotic process, there is a steady increase in this risk after the transition to menopause ( 2 ). This is mostly evident in women with early menopause (EM

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Christos Tsatsanis Department of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Crete, Greece
Molecular Reproductive Research Group, Department of Translational Medicine, Lund University, Malmö, Sweden
Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Greece

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Angel Elenkov Molecular Reproductive Research Group, Department of Translational Medicine, Lund University, Malmö, Sweden
Reproductive Medicine Centre, Skåne University Hospital Malmö, Malmö, Sweden

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Irene Leijonhufvud Reproductive Medicine Centre, Skåne University Hospital Malmö, Malmö, Sweden

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Katerina Vaporidi Molecular Reproductive Research Group, Department of Translational Medicine, Lund University, Malmö, Sweden

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Åsa Tivesten Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

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Aleksander Giwercman Molecular Reproductive Research Group, Department of Translational Medicine, Lund University, Malmö, Sweden
Reproductive Medicine Centre, Skåne University Hospital Malmö, Malmö, Sweden

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to be regulated by sex hormones. BAFF suppression by testosterone has been demonstrated in animal studies and indirectly in humans when comparing men with high and low testosterone levels ( 4 ). In contrast, estrogens have been demonstrated to induce

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Michael C Velarde Institute of Biology, College of Science, University of the Philippines Diliman, Quezon, Metro Manila, Philippines

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Mikaela Erlinda M Bucu Department of Obstetrics and Gynecology, College of Medicine, University of the Philippines Manila, Metro Manila, Philippines

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Maria Antonia E Habana Department of Obstetrics and Gynecology, College of Medicine, University of the Philippines Manila, Metro Manila, Philippines

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Introduction Endometriosis is a debilitating, chronic, inflammatory, progressive, estrogen-dependent disease characterized by the presence of endometrial tissues outside the uterine cavity, presenting clinically as dysmenorrhea, dyspareunia

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Giuseppe Grande Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Andrea Graziani Department of Medicine, University of Padova, Padova, Italy

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Antonella Di Mambro Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Riccardo Selice Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Alberto Ferlin Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
Department of Medicine, University of Padova, Padova, Italy

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indirectly through the estrogen receptor (ER) after the transformation of testosterone to estradiol by the aromatase enzyme ( 32 , 37 ). In detail, testosterone modulates bone metabolism throughout life in males ( 38 ). The increase in the production of

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Shiori Minabe Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan

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Kinuyo Iwata Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

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Youki Watanabe Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

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Hirotaka Ishii Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

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Hitoshi Ozawa Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Faculty of Health Science, Bukkyo University, Kyoto, Japan

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), postnatal estrogen exposure ( 29 , 30 ), and perinatal overnutrition ( 31 ) affect the ARC Kiss1 expression and/or thereby pulsatile luteinizing hormone (LH) secretion in adulthood. Furthermore, undernutrition during postnatal periods alters pubertal

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Alan D Rogol Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

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gonadotropin-inhibiting effects of placental estrogens. The HPG axis becomes progressively more active but with different kinetics in boys and girls (reviewed in ( 3 )). The LH levels are higher in boys than girls and the opposite is true for FSH. LH levels

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Theodoros Karampitsakos Third Department of Obstetrics and Gynecology, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Fotini Kanouta Unit of Endocrinology, Diabetes Mellitus and Metabolism, First Department of Obstetrics and Gynecology, ALEXANDRA University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Christos Chatzakis Second Department of Obstetrics and Gynecology, IPPOKRATEIO General Hospital of Thessaloniki, Aristotle, University of Thessaloniki, Athens, Greece

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Vassilios Bakoulas Athens, Greece

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Alexandros Gryparis Department of Speech and Language Therapy, University of Ioannina, Ioannina, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Petros Drakakis Third Department of Obstetrics and Gynecology, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Djuro Macut Department of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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George Mastorakos Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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adrenals, leading thus to the production of cortisol and DHEAS ( Fig. 2 ). In humans and primates, at term, the placenta does not express cytochrome P450c17, an enzyme necessary for estrogen synthesis from progesterone. In placental syncytiotrophoblast

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