Review and Recommendations on Management of Adult Female Thalassemia Patieνts With Hypogonadism Based on Literature Review and Experience of Icet-a Network Specialists

Abstract

BackgroundMulti-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.MethodsIn 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.ResultsThe 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.ConclusionsDoctors 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.

The Influence of Cardiovascular Risk Factors and Hypogonadism on Cardiac Outcomes in an Aging Population of Beta-Thalassemia Patients

“…On top of that, splenectomies have a well-known role in increasing susceptibility to infections and the risk of developing pulmonary hypertension [1]; Further studies are needed to better clarify if the absence of a spleen is directly connected to the hypophysis iron deposition, but our data might represent a red flag for follow-up with this kind of patient, even if, by now, the traditional cardiovascular risk scores may appear low [22]. These considerations are important, since there are many reports of a safe and effective sex hormone replacement therapy in this population [23][24][25] but also because-at least in men-hormonal therapy could also induce adverse events and impact coronary plaque volume [23,26].…”

Good Clinical Practice of the Italian Society of Thalassemia and Haemoglobinopathies (SITE) for the Management of Endocrine Complications in Patients with Haemoglobinopathies

“…Progestin is added to oestrogen replacement therapy in a sequential cyclic manner for about 12–14 days a month in non-hysterectomized women. Recently, natural micronized progesterone, made up of smaller particles that facilitate absorption, has come into use for oral (200 mg/day) or intravaginal administration; it is supposed to have better tolerability, lower thrombotic risk, and fewer effects on lipid metabolism as compared to synthetic progestins [ 30 , 31 , 32 ].…”

Growth and Endocrine Function in Tunisian Thalassemia Major Patients

“…In female patients, hypogonadism is clinically diagnosed by the absence of pubertal development or discontinuation or regression of the maturation of secondary sex characteristics. 20 Low serum concentrations of sex hormones and gonadotropins confirm the diagnosis. Several questions were asked about their diagnosis, their central or peripheral origin and their reversibility to the intensification of the iron chelating treatment.…”

“…Hypogonadotropic hypogonadism, is the most frequent endocrinopathy in patients with transfusion-dependent thalassemia. 19 , 20 In male patients, clinical presentations of hypogonadotropic hypogonadism include lack, delay, and/or block of pubertal sexual maturation and, in adult life, decreased libido, erectile dysfunction, worsened sense of well-being, and lower quality of life. Spermatogenesis is impaired, and the volume of ejaculate is decreased.…”