title: Review and Recommendations on Management of Adult Female Thalassemia Patients with Hypogonadism based on Literature Review and Experience of ICET-A Network Specialists.
abstract: BACKGROUND
  Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists. The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper, practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed.
  
  
  METHODS
  In March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network.
  
  
  RESULTS
  The completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism, and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centers (68.7%). A wide range of COCs was used with different progestin contents. In general, the patients' compliance to treatment was reported as good in 81.2 % of centers. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centers.
  
  
  CONCLUSIONS
  Doctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming of attaining a full pubertal development.
authors.affiliation: Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Sanctis
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Hamad General Hospital Doha, Qatar and Department of Pediatrics, Division of Endocrinology, Alexandria University Children's Hospital, Alexandria, Egypt.
authors.forename: Ashraf T
authors.initials: AT
authors.lastname: Soliman
authors.affiliation: Department of Pediatrics, Ain Shams University, Cairo, Egypt.
authors.forename: Heba
authors.initials: H
authors.lastname: Elsedfy
authors.affiliation: Endocrinology and Diabetes Department of Elias Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Alice
authors.initials: A
authors.lastname: Albu
authors.affiliation: Head Division of Pediatric Hematology Oncology, Deputy Chair of Hematology & Head Section of Hematology Research Lab, King Fahd Medical Research Center Department of Hematology Faculty of Medicine, King Abdulaziz University Jeddah, Kingdom of Saudi Arabia.
authors.forename: Soad
authors.initials: S
authors.lastname: Al Jaouni
authors.affiliation: Thalassemia Unit, Maternal and Child Department, Garibaldi Hospital, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Anastasi
authors.affiliation: Thalassemia Unit, Cosenza, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bisconte
authors.affiliation: Director of Thalassemia Diagnosis Center of Mediterranean Blood Diseases Foundation Antalya, Turkey.
authors.forename: Duran
authors.initials: D
authors.lastname: Canatan
authors.affiliation: Thalassemia Unit, Nicosia, Cyprus.
authors.forename: Soteroula
authors.initials: S
authors.lastname: Christou
authors.affiliation: Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman & Visiting Scholar, Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch 7600, South Africa.
authors.forename: Shahina
authors.initials: S
authors.lastname: Daar
authors.affiliation: Emeritus Director in Pediatrics, Children's Hospital "Santobono-Pausilipon", Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Maio
authors.affiliation: Department of Pediatrics, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Kholy
authors.affiliation: Department of Pediatrics, Endocrinology Unit, Alexandria University Children's Hospital, Egypt and Child Health Department, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman.
authors.forename: Doaa
authors.initials: D
authors.lastname: Khater
authors.affiliation: Department of Pediatrics, Hematology Unit, Faculty of Medicine, University of Alexandria, Egypt and Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elshinawy
authors.affiliation: Çukurova University, Medical Faculty, Department of Pediatric Hematology, Adana, Turkey.
authors.forename: Yurdanur
authors.initials: Y
authors.lastname: Kilinc
authors.affiliation: Pediatric Unit, Adria, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mattei
authors.affiliation: Internal Medicine, Endocrinology and Metabolism, Department of Medicine King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Hala H
authors.initials: HH
authors.lastname: Mosli
authors.affiliation: Thalassemia Unit, Gela, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Quota
authors.affiliation: Immunohematology and Blood Bank Unit, OORR Foggia, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roberti
authors.affiliation: Pediatric Hemato-Oncology Unit, Christian Medical College and Hospital, Ludhiana Punjab, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sobti
authors.affiliation: Head of Pediatric Endocrine Unit, Department of Child Health, Sultan Qaboos University Hospital, Al-Khoud, Sultanate of Oman.
authors.forename: Saif Al
authors.initials: SA
authors.lastname: Yaarubi
authors.affiliation: Thalassemia Unit, Umberto 1° Hospital, Siracusa, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Canpisi
authors.affiliation: First Department of Paediatrics, University of Athens, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Kattamis
keywords: Thalassemia; benefits and disadvantages; hormone replacement therapy; hypogonadism