Scientific Letter
Monitoring of the treatment of hypogonadotropic hypogonadism in the infant
Monitorización del tratamiento del hipogonadismo hipogonadotropo en el lactante
María Álvarez Casaño
, Juan Pedro López Siguero
Corresponding author
Servicio de Endocrinología Pediátrica, Hospital Regional Universitario de Málaga, Málaga, Spain
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Adjust fed products to the patient's age.</p> <p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">BF, breastfeeding; CM, cow's milk.</p> <p id="spar0110" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">1</span> Simple biscuits, such as María biscuits (no chocolate, custard, etc.). To feed infants, they can be puréed with fruit.</p> <p id="spar0115" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">2</span> Adding fresh fruit or sweetening lightly with some milk of sugar is acceptable.</p> <p id="spar0120" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">3</span> In children that continue to breastfeed, introduction of cow's milk will be delayed until breastfeeding is discontinued or supplementation becomes necessary.</p> <p id="spar0125" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">4</span> Extensively hydrolysed formula, hydrolysed rice protein formula or soy-based formula.</p> <p id="spar0130" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">5</span> Eventually, introduce a lactose-free formula, and later switch to an adapted formula.</p> <p id="spar0135" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">6</span> In children that are not fed special formulas (for instance, fed plant-based milks) CMP could be reintroduced with low-fat milk (to facilitate acceptance), switching to whole milk 2 weeks later.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Beatriz Espín Jaime, Juan J. 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This period of “axis activation” lasts approximately 6 months in boys and 2–3 years in girls. In males, this is a critical period not only for the development of external genitalia, but also for the differentiation of Sertoli cells and therefore for future fertility.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Since female patients do not present any phenotypic abnormalities, diagnosis at this age is difficult unless they exhibit panhypopituitarism. In any case, at this age treatment is only given to male patients.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment with gonadotropins is the most natural treatment that can be used in the first year of life. The first case of treatment in a male was reported in 2002,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> with initiation of treatment at age 8 months and a good growth response in the testicle, but not in the penis, which required further treatment with testosterone at a later age.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Administration of recombinant human follicle-stimulating hormone (FSH) and human chorionic gonadotropin (HCG) in the first 6–7 months of life stimulates Sertoli cell function (the effect can be assessed by measuring the levels of inhibin B and anti-Müllerian hormone [AMH]) and Leydig cell function while these cells exist (assessing the effect by measuring testosterone or insulin-like 3 [INSL3] protein levels).</p><p id="par0040" class="elsevierStylePara elsevierViewall">In many cases, the micropenis in these infants is associated with cryptorchidism and small testicular volume. Treatment with gonadotropins at this age can increase intratesticular gonadotropin concentrations without risk of inducing spermatogenesis or a negative impact in the number of Sertoli cells, as these do not express androgen receptors until age 5 years. Treatment with FSH can increase testicular volume (as well as AMH and inhibin B levels) and treatment with HCG can increase levels of testosterone and INSL3.</p><p id="par0045" class="elsevierStylePara elsevierViewall">However, there is still little experience with this pharmacologic approach, and there are no established protocols for its dosage or durations.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment must be initiated as early as possible (thus the importance of early diagnosis), ideally within 6 months from birth. Although the literature on dosage is scarce, it has been proposed that treatment be initiated with a combination of FSH (37.5–75<span class="elsevierStyleHsp" style=""></span>IU) administered subcutaneously 2 or 3 times a week and HCG (250–500 UI) administered subcutaneously twice a week.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Treatment is maintained until at least age 6–7 months, the maximum clinical effectiveness is achieved (normal testicular volume and penile length) or testosterone levels decrease (which would signal a decrease in the population of Leydig cells).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">We now describe the first clinical case, corresponding to a newborn that presented with hypoglycaemia and micropenis and received a diagnosis of hypogonadotropic hypogonadism. Treatment with gonadotropins (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) was initiated at age 1 month and a half and maintained until 6 months, when there was a marked decrease in testosterone levels despite the continued administration of gonadotropins. This decrease marks the end of “minipuberty” and thus the ideal time to end treatment.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The second case corresponds to another male patient that also received a diagnosis of hypogonadotropic hypogonadism that started treatment with HCG and FSH at age 15 days. We monitored treatment by measuring the levels of testosterone, which exhibited a sharp elevation at age 5 months, upon which the dose given was halved. There was another sudden drop in testosterone at age 8 months, which led to discontinuation of treatment (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">To conclude, while further studies are required, it is reasonable to assert that treatment of hypogonadotropic hypogonadism should start as early as possible with the aim of simulating the “minipuberty” stage. As for its monitoring, in addition to observing the growth of the penis and testes, measurement of testosterone levels is useful, as they can provide an accurate marker of the end of minipuberty and therefore of the right time to discontinue treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Álvarez Casaño M, López Siguero JP. Monitorización del tratamiento del hipogonadismo hipogonadotropo en el lactante. An Pediatr (Barc). 2019;90:190–192.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1.5 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3.5 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 year and 2 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 year and 10 months \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testosterone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.04<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.62<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.81<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.025<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.07<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Penis size \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testicular volume \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Initiation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unchanged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Discontinued \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gonadotropins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HCG 250<span class="elsevierStyleHsp" style=""></span>IU<br>2 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HCG 250<span class="elsevierStyleHsp" style=""></span>IU<br>2 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FSH 37.5<span class="elsevierStyleHsp" style=""></span>IU 3 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FSH 37.5 IU3 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1977061.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution and outcome of case 1.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">15 days \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4.5 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">5.5 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">8 months \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testosterone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.56<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.78<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03<span class="elsevierStyleHsp" style=""></span>ng/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Penis size \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testicular volume \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><1<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>mL<br>Scrotum with rugae and deeply pigmented \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Initiation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dose reduction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unchanged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Discontinued HCG Y FSH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gonadotropins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HCG 500<span class="elsevierStyleHsp" style=""></span>IU<br>2 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HCG 250<span class="elsevierStyleHsp" style=""></span>IU<br>2 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Initiation of GH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FSH 75<span class="elsevierStyleHsp" style=""></span>IU 3 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FSH 37.5<span class="elsevierStyleHsp" style=""></span>IU 3 times/wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1977060.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evolution and outcome of case 2.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypogonadismes hypogonadotrophiques congénitaux et syndrome de Kallmann chez l’homme" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Ghervan" 1 => "J. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.lpm.2013.12.008" "Revista" => array:6 [ "tituloSerie" => "Presse Med" "fecha" => "2014" "volumen" => "43" "paginaInicial" => "152" "paginaFinal" => "161" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24456696" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation of the hypothalamic-pituitary-gonadal axis in infancy: minipuberty" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T. Kuiri-Hänninen" 1 => "U. Sankilampi" 2 => "L. Dunkel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000362414" "Revista" => array:6 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2014" "volumen" => "82" "paginaInicial" => "73" "paginaFinal" => "80" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25012863" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0045" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.M. Main" 1 => "I.M. Schmidt" 2 => "J. Toppari" 3 => "N.E. Skakkebæk" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2002" "volumen" => "146" "paginaInicial" => "75" "paginaFinal" => "79" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11751071" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0050" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Different medications for hypogonadotropic hypogonadism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Rastrelli" 1 => "L. Vignozzi" 2 => "M. Maggi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Endocr Dev" "fecha" => "2016" "volumen" => "30" "paginaInicial" => "60" "paginaFinal" => "78" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Bouvattier" 1 => "L. Maione" 2 => "J. Bouligand" 3 => "C. Dodé" 4 => "A. Guiochon-Mantel" 5 => "J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 11 | 19 |
| 2024 October | 48 | 33 | 81 |
| 2024 September | 58 | 44 | 102 |
| 2024 August | 56 | 62 | 118 |
| 2024 July | 42 | 38 | 80 |
| 2024 June | 54 | 51 | 105 |
| 2024 May | 44 | 33 | 77 |
| 2024 April | 47 | 38 | 85 |
| 2024 March | 50 | 29 | 79 |
| 2024 February | 35 | 29 | 64 |
| 2024 January | 38 | 19 | 57 |
| 2023 December | 43 | 29 | 72 |
| 2023 November | 46 | 37 | 83 |
| 2023 October | 35 | 30 | 65 |
| 2023 September | 32 | 27 | 59 |
| 2023 August | 38 | 13 | 51 |
| 2023 July | 44 | 24 | 68 |
| 2023 June | 27 | 22 | 49 |
| 2023 May | 39 | 30 | 69 |
| 2023 April | 29 | 11 | 40 |
| 2023 March | 55 | 21 | 76 |
| 2023 February | 46 | 22 | 68 |
| 2023 January | 20 | 24 | 44 |
| 2022 December | 44 | 36 | 80 |
| 2022 November | 55 | 31 | 86 |
| 2022 October | 65 | 43 | 108 |
| 2022 September | 61 | 35 | 96 |
| 2022 August | 53 | 45 | 98 |
| 2022 July | 35 | 52 | 87 |
| 2022 June | 51 | 28 | 79 |
| 2022 May | 73 | 39 | 112 |
| 2022 April | 43 | 32 | 75 |
| 2022 March | 102 | 57 | 159 |
| 2022 February | 63 | 44 | 107 |
| 2022 January | 74 | 40 | 114 |
| 2021 December | 61 | 43 | 104 |
| 2021 November | 70 | 56 | 126 |
| 2021 October | 86 | 94 | 180 |
| 2021 September | 64 | 47 | 111 |
| 2021 August | 47 | 47 | 94 |
| 2021 July | 52 | 23 | 75 |
| 2021 June | 53 | 34 | 87 |
| 2021 May | 59 | 34 | 93 |
| 2021 April | 144 | 63 | 207 |
| 2021 March | 95 | 33 | 128 |
| 2021 February | 56 | 8 | 64 |
| 2021 January | 50 | 22 | 72 |
| 2020 December | 55 | 18 | 73 |
| 2020 November | 52 | 20 | 72 |
| 2020 October | 47 | 20 | 67 |
| 2020 September | 48 | 36 | 84 |
| 2020 August | 53 | 20 | 73 |
| 2020 July | 95 | 31 | 126 |
| 2020 June | 54 | 18 | 72 |
| 2020 May | 39 | 12 | 51 |
| 2020 April | 35 | 9 | 44 |
| 2020 March | 19 | 11 | 30 |
| 2020 February | 23 | 15 | 38 |
| 2020 January | 39 | 8 | 47 |
| 2019 December | 54 | 12 | 66 |
| 2019 November | 34 | 7 | 41 |
| 2019 October | 32 | 18 | 50 |
| 2019 September | 29 | 14 | 43 |
| 2019 August | 43 | 21 | 64 |
| 2019 July | 32 | 21 | 53 |
| 2019 June | 30 | 16 | 46 |
| 2019 May | 27 | 27 | 54 |
| 2019 April | 49 | 25 | 74 |
| 2019 March | 74 | 30 | 104 |
| 2019 February | 13 | 10 | 23 |
Show all
