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Daniela Leite de Oliveira Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil

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Camila Hirotsu Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil

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Sergio Tufik Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil

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Monica Levy Andersen Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil

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disorders, which can lead to increased pain sensitivity ( Dhesi et al . 2002 , Orme et al . 2013 , Lachmann et al . 2015 ). Regarding the mechanisms of pain sensitization, vitamin D seems to stimulate anti-inflammatory processes in some cases and thus

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Donato Calabrese
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Silvia Giatti
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Simone Romano
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Carla Porretta-Serapiglia Section of Biomedicine and Endocrinology, Neuromuscular Disease Unit, Department of Pharmacy and Center of Excellence for Biomedical Research, Instituto Cajal, Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy

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Roberto Bianchi Section of Biomedicine and Endocrinology, Neuromuscular Disease Unit, Department of Pharmacy and Center of Excellence for Biomedical Research, Instituto Cajal, Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy

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Marco Milanese Section of Biomedicine and Endocrinology, Neuromuscular Disease Unit, Department of Pharmacy and Center of Excellence for Biomedical Research, Instituto Cajal, Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy

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Giambattista Bonanno Section of Biomedicine and Endocrinology, Neuromuscular Disease Unit, Department of Pharmacy and Center of Excellence for Biomedical Research, Instituto Cajal, Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy

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Donatella Caruso
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Barbara Viviani
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Fabrizio Gardoni
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Luis Miguel Garcia-Segura Section of Biomedicine and Endocrinology, Neuromuscular Disease Unit, Department of Pharmacy and Center of Excellence for Biomedical Research, Instituto Cajal, Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy

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Roberto Cosimo Melcangi
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Introduction Neuropathic pain is a common consequence of diabetes mellitus that strongly impairs quality of life ( Smith & Argoff 2011 , Tesfaye & Selvarajah 2012 ). Neuroinflammation, altered neurotransmission mediated by excitatory amino acids

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Jing Li Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

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Pan-Pan Zhao Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

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Ting Hao Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

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Dan Wang Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

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Yu Wang Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

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Yang-Zi Zhu Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

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Yu-Qing Wu Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
Department of Anesthetic Pharmacology, Xuzhou Medical University, Xuzhou, China

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Cheng-Hua Zhou Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China

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Introduction Neuropathic pain can be defined as an abnormal pain sensation in the peripheral or central nervous system after injuries. It is caused by dysfunction in the peripheral or central nervous system without peripheral nociceptor

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M. Caleffi
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I. S. Fentiman
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G. M. Clark
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D. Y. Wang
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J. Needham
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K. Clark
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A. La Ville
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B. Lewis
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ABSTRACT

As part of a controlled trial of the use of tamoxifen for the treatment of mastalgia, some of the metabolic and haematological effects of this agent were measured. A panel of haemostatic variables including prothrombin time, kaolin cephalin clotting time, fibrinogen, euglobulin lysis time, factor VII, factor VIII, protein C and anti-thrombin III were determined. In addition, levels of sex hormone-binding globulin and both total and free oestradiol were estimated. No alteration in clotting function was found during the administration of tamoxifen, although hepatic function did alter during this period with an increase in concentration of sex hormone-binding globulin. There was a significant increase in total oestradiol and free oestradiol although the percentage of biologically available free oestradiol fell slightly during the course of tamoxifen treatment. There was a slight reduction in low-density lipoprotein cholesterol with an increase in HDL2, a subclass of high-density lipoprotein (HDL) cholesterol, consistent with an oestrogen-agonist effect. These data suggest that tamoxifen administration does not adversely influence haemostatic mechanisms or lipoprotein metabolism in the short term.

J. Endocr. (1988) 119, 335–339

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Emma Wilson Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
Simons Initiative for the Developing Brain, The University of Edinburgh, Edinburgh, UK

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Fiona J Ramage Department of Systems Medicine, School of Medicine, University of Dundee, Dundee, UK

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Kimberley E Wever Department of Anesthesiology, Pain and Palliative Care, Radboud University Medical Center, Nijmegen, The Netherlands

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Emily S Sena Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK

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Malcolm R Macleod Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK

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Gillian L Currie Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK

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In biomedicine and many other fields, there are growing concerns around the reproducibility of research findings, with many researchers being unable to replicate their own or others’ results. This raises important questions as to the validity and usefulness of much published research. In this review, we aim to engage researchers in the issue of research reproducibility and equip them with the necessary tools to increase the reproducibility of their research. We first highlight the causes and potential impact of non-reproducible research and emphasise the benefits of working reproducibly for the researcher and broader research community. We address specific targets for improvement and steps that individual researchers can take to increase the reproducibility of their work. We next provide recommendations for improving the design and conduct of experiments, focusing on in vivo animal experiments. We describe common sources of poor internal validity of experiments and offer practical guidance for limiting these potential sources of bias at different experimental stages, as well as discussing other important considerations during experimental design. We provide a list of key resources available to researchers to improve experimental design, conduct, and reporting. We then discuss the importance of open research practices such as study preregistration and the use of preprints and describe recommendations around data management and sharing. Our review emphasises the importance of reproducible work and aims to empower every individual researcher to contribute to the reproducibility of research in their field.

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Carmen Corciulo Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Julia M Scheffler Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Piotr Humeniuk Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Alicia Del Carpio Pons Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Alexandra Stubelius Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

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Ula Von Mentzer Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

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Christina Drevinge Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Aidan Barrett Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Sofia Wüstenhagen Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Matti Poutanen Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Turku, Finland

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Claes Ohlsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Department of Drug Treatment, Sahlgrenska University Hospital, Gothenburg, Sweden

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Marie K Lagerquist Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Ulrika Islander Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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associated with structural subchondral bone damage, increased pain sensitivity also in body parts that are not directly affected by the disease, and mild inflammation of the synovium ( Loeser et al. 2012 ). OA affects more than 240 million people globally

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Ann T Hanna-Mitchell Departments of Medicine-Renal Electrolyte Division, Pharmacology and Chemical Biology, Department of Veterinary Clinical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Amanda Wolf-Johnston Departments of Medicine-Renal Electrolyte Division, Pharmacology and Chemical Biology, Department of Veterinary Clinical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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James R Roppolo Departments of Medicine-Renal Electrolyte Division, Pharmacology and Chemical Biology, Department of Veterinary Clinical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Tony C A Buffington Departments of Medicine-Renal Electrolyte Division, Pharmacology and Chemical Biology, Department of Veterinary Clinical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Lori A Birder Departments of Medicine-Renal Electrolyte Division, Pharmacology and Chemical Biology, Department of Veterinary Clinical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Departments of Medicine-Renal Electrolyte Division, Pharmacology and Chemical Biology, Department of Veterinary Clinical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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stress and symptom exacerbation in bladder diseases, such as IC/PBS. IC/PBS is characterized by urinary frequency, urgency, and pelvic pain ( Hanno et al . 2010 ) and patients are reported to display symptom exacerbation and a heightened sensitivity to

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Taisuke Mori Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Fumitake Ito Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Hiroshi Matsushima Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Osamu Takaoka Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Akemi Koshiba Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Yukiko Tanaka Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Izumi Kusuki Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Jo Kitawaki Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

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Introduction Endometriosis is defined as the presence of endometrium-like tissues at extra-uterine sites. Clinical symptoms associated with endometriosis include pelvic pain, dysmenorrhea, dyspareunia, and infertility ( Giudice 2010 ). There

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D. W. LINCOLN
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B. A. CROSS
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SUMMARY

The responses of septal, preoptic and hypothalamic neurones to pain, cold, changes in ocular illumination and probing of the cervix were recorded in adult female rats under light urethane anaesthesia. Responses in rats with light-induced persistent oestrus were compared with those obtained after ovariectomy, and after ovariectomy with oestrogen treatment.

The majority of units in the lateral hypothalamic area were excited by pain, cold and cervical stimuli, whereas in the lateral septal area most were inhibited. The numbers of units in the anterior hypothalamic and preoptic areas that displayed excitation to these stimuli were approximately equal to those showing inhibition.

The time-course of the responses to pain, cold and cervical stimuli of most hypothalamic and septal units closely corresponded to that of the associated EEG activation (frontal cortex), suggesting that they were non-specific arousal effects. Other responses, usually of brief duration, were not correlated with EEG changes.

Endogenous and exogenous oestrogen increased the percentage of units in the lateral and anterior hypothalamic areas that were inhibited by the pain, cold and cervical stimuli, and decreased the number in the lateral septal area. Oestrogen enhanced the responsiveness of preoptic units to the cervical stimulus, but depressed their responsiveness to pain and cold.

Hypothalamic units inhibited by the pain stimulus had mean 'spontaneous' firing rates of 4–5 spikes/sec. and those which were excited had rates of 1–2/sec.

Light-sensitive units were found mainly in the lateral septal and anterior hypothalamic areas. The usual form of the response was a brief 'on-off' or 'off-on' discharge.

The results are discussed in relation to the central nervous control of ovulation.

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M. C. P. Rees
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V. Di Marzo
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J. R. Tippins
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H. R. Morris
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A. C. Turnbull
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ABSTRACT

Endometrium and myometrium were collected at hysterectomy from 21 women with measured menstrual blood loss. Eight women complained of dysmenorrhoea and the remaining 13 had pain-free periods. Specimens were obtained throughout the menstrual cycle (menstrual, n = 5; follicular, n = 3; early luteal, n = 3; mid-luteal, n = 5; late luteal, n = 4). Leukotriene C4, leukotriene D4 and leukotriene E4 release were examined using a short-term incubation technique. Endometrial leukotriene release, which was always significantly greater than myometrial release, changed throughout the menstrual cycle and the highest concentrations were found during menstruation. Endometrial, but not myometrial, leukotriene concentrations were significantly higher in tissues obtained from women with a complaint of dysmenorrhoea compared with those in tissue from pain-free women. No correlation was found between leukotriene release in either endometrium or myometrium and menstrual blood loss (range 15–457 ml).

J. Endocr. (1987) 113, 291–295

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