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Spanish Consensus on Premature Menopause

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Spanish Consensus on Premature Menopause Maturitas 80 (2015) 220–225 Contents lists available at ScienceDirect Maturitas jou rnal homepage: www.elsevier.com/locate/maturitas Spanish consensus on premature menopause a,∗ a b c d Nicolás Mendoza , M Dolores Juliá , Daniela Galliano , Pluvio Coronado , e f f g h Begona˜ Díaz , Juan Fontes , José Luis Gallo , Ana García , Misericordia Guinot , i j k j l Merixtell Munnamy , Beatriz Roca , Manuel Sosa , Jordi Tomás , Plácido Llaneza , m Rafael Sánchez-Borrego a University of Granada, Obstetric and Gynecologic, Granada, Spain b Hospital Universitario la Fe de Valencia, Spain c Instituto Valenciano de Infertilidad (IVI), Barcelona, Spain d University of Madrid (Complutense), Obstetric and Gynecologic, Hospital Clínico San Carlos, Madrid, Spain e Complejo Hospitalario Universitario de Albacete, Spain f Hospital Virgen de las Nieves de Granada, Spain g Instituto Valenciano de Oncología, Spain h Hospital Clinic Barcelona, Spain i Sant Feliu de Llobregat, Barcelona, Spain j Hospital Universitari Mutua Terrassa, Spain k Hospital Materno-Infantil de Canarias, Spain l University of Oviedo, Obstetric and Gynecologic, Hospital Central de Asturias, Spain m Clínica Diatros, Barcelona, Spain a r t i c l e i n f o a b s t r a c t Article history: Introduction: While we recognise that the term premature menopause is more accepted by most non- Received 18 September 2014 specialist health care providers and by the general population, ‘primary ovarian insufficiency’ (POI) is Received in revised form 3 November 2014 currently considered the most apposite term to explain the loss of ovarian function, because it better Accepted 12 November 2014 explains the variability of the clinical picture, does not specify definitive failure, and highlights the specific ovarian source. Its pathogenesis involves a congenital reduction in the number of primordial follicles, poor Keywords: follicle recruitment, or accelerated follicular apoptosis. However, its cause is unknown in most cases. Primary ovarian insufficiency Aim: This guide analyses the factors associated with the diagnosis and treatment of POI and provides Premature menopause recommendations on the most appropriate diagnostic and therapeutic measures for women under 40 Hormonal therapy years of age who experience POI. Fertility preservation Fertility treatments Methodology: A panel of experts from various Spanish scientific societies related to POI (Spanish Osteoporosis Menopause Society, Spanish Fertility Society, and Spanish Contraception Society) met to reach a con- sensus on these issues. Results: Hormonal therapy (HT) is considered the treatment of choice to alleviate the symptoms of hypoe- strogenism and to prevent long-term consequences. We suggest that HT should be continued until at least age 51, the average age at natural menopause. The best treatment to achieve pregnancy is oocyte/embryo donation. If a patient is to undergo treatment that will reduce her fertility, she should be informed of this issue and the available techniques to preserve ovarian function, mainly vitrification of oocytes. © 2014 Elsevier Ireland Ltd. All rights reserved. ∗ Corresponding author at: Maestro Montero, 21, 18004 Granada, Spain. Tel.: +34 958120206. E-mail addresses: [email protected] (N. Mendoza), [email protected] (M.D. Juliá), daniela [email protected] (D. Galliano), [email protected] (P. Coronado), bego [email protected] (B. Díaz), [email protected] (A. García), [email protected] (M. Guinot), [email protected] (M. Munnamy), [email protected] (B. Roca), [email protected] (M. Sosa), [email protected] (J. Tomás), [email protected] (P. Llaneza), [email protected] (R. Sánchez-Borrego). http://dx.doi.org/10.1016/j.maturitas.2014.11.007 0378-5122/© 2014 Elsevier Ireland Ltd. All rights reserved. N. Mendoza et al. / Maturitas 80 (2015) 220–225 221 Table 1 1. Introduction Most common causes of non-iatrogenic POI. Different diagnostic terminology has been used in relation to the • Turner syndrome (XO 45) is the most common genetic cause. Sufferers have normal early follicular levels but loss of ovarian function, including premature or early menopause, Genetic accelerated follicular depletion premature or early ovarian failure, and the most recent term, pri- • FMR1 (Fragile X Mental retardation 1) premutation mary ovarian insufficiency (POI). The last is currently considered the • Other chromosome X abnormalities: mutations of FOXL2, most apposite because it better allows for the variability of the clin- NR5A1, BMP15, FSHR, and Gs alpha genes, and of ical picture, including its rare reversibility and the fact that it does steroidogenic enzymes not necessarily involve definitive failure, and because it specifically • Galactose-1-phosphate uridyltransferase deficiency • highlights the ovarian source of the problem [1]. Carbohydrate-deficient glycoprotein deficiency Metabolic • Although we have no data on its incidence in Spain, records indi- 17 alpha-hydroxylase/17, 20 desmolase deficiency Mutations of the aromatase gene cate that the condition may have a higher incidence than previously • thought and may be present in a young patient who complains of Polyglandular autoimmune syndrome • Hypothyroidism cycle disorders. Its incidence is 1/250 among women aged 35 years • Type I diabetes mellitus and 1/100 among women aged 40 years [2,3]. Moreover, there is • Myasthenia gravis evidence that the incidence may be increasing above 1% due to • Systemic lupus erythematosus iatrogenic causes [4]. • Addison’s disease • The objective of this guide is to analyse the factors associated Thrombocytopenic purpura Autoimmune • Vitiligo with the diagnosis and treatment of POI and to recommend the • Alopecia most appropriate diagnostic and therapeutic measures for women • Pernicious anaemia or autoimmune anaemia under 40 years of age. • Rheumatoid arthritis • Crohn’s disease • Sjögren’s syndrome 2. Methods • Primary biliary cirrhosis Infectious • Viral infections (human immunodeficiency virus, A panel of experts from various Spanish scientific societies varicella), tuberculosis, malaria, shigellosis related to POI (Spanish Menopause Society, Spanish Fertility Soci- Other • Women of Chinese race or Hispanic origin [5] ety, Spanish Contraception Society and Spanish Medical-Oncologic • causes Environmental toxins (e.g. tobacco, dioxins) [6,7] Society) met to reach a consensus on these issues. Each society chose its participants. Participants were responsible for review- ing and drafting each part of this guide. All authors were involved in the writing of the statement and approved the final version. The consensus panel considered it appropriate to develop its own severe in younger patients and when the presentation is acute (e.g. recommendations based on the GRADE (Grading of Recommen- after surgical menopause). Because there is still some hormonal dations Assessment, Development and Evaluation) system for the production left in more than half of POI cases, the absence of these elaboration of clinical practice guidelines and to classify the qual- symptoms should not rule out its diagnosis [13]. ity of the evidence and the strength of the recommendations In addition, POI is considered an independent risk factor for (http://cebgrade.mcmaster.ca/). cardiovascular disease (CVD), osteoporosis (OP) [14,15], and mood disorders, as well as cognitive impairment [16]. Autoimmune POI (see Table 1), as well as the associated 3. Pathogenesis hypoestrogenism itself, decreases certain endocrine functions (e.g. growth hormone) and induces a predisposition to other Onset of the condition is spontaneous and its cause is unknown endocrinopathies (mainly thyroid and adrenal) [17]. in most cases. It may occur after chemotherapy (CT), surgical treat- ment or radiotherapy (RT). Its pathogenesis involves a congenital reduction in the number of primordial follicles, poor follicle recruit- ment, or accelerated follicular apoptosis. The most common causes 5. Diagnosis of non-iatrogenic POI are shown in Table 1. Unfortunately, we do not have specific markers for the diagnosis 3.1. Iatrogenic POI of POI, and most guidelines use the following triad: a woman under 40 with secondary oligomenorrhea or amenorrhea of more than Cancer treatment in young women is often associated with POI 3 months’ duration, and follicle-stimulating hormone (FSH) levels [8], tending towards greater intensity with higher treatment expo- above 40 IU/l [1]. sure or a greater surgically excised area. After RT, the risk of POI At the initial clinical evaluation, transvaginal ultrasound is rises in direct relation to the age of the patient, the dose received, recommended. Although the cause will typically not be known, and whether it is directed to the pelvis [9]. POI secondary to CT tests for chromosomal, genetic and immunological, disorders and depends on the type of drug, its dose, and the age of the patient. infection will be requested individually (see the POI Diagnostic Alkylating agents, often used in the treatment of lymphomas and Algorithm in Fig. 1). certain autoimmune diseases, are the most damaging to oocytes A study of ovarian reserve is essential in women with a and granulosa cells [10–12]. desire for pregnancy, preferably by ultrasound count of antral follicles and measurement of anti-müllerian hormone (AMH). Although the determination of AMH levels has no utility at present 4. Clinical symptoms beyond reproductive prognosis, mathematical models are being designed that incorporate this test in predicting age at menopause In the short,
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