Academic literature on the topic 'Pubertal induction'

Puberty is the period during which we attain adult secondary sexual characteristics and reproductive capability. Its onset depends upon reactivation of pulsative GNRH, secretion from its relative quiescence during childhood, on the background of intact potential for pituitary–gonadal function. This review is intended: to highlight those current practices in diagnosis and management that are evidence based and those that are not; to help clinicians deal with areas of uncertainty with reference to physiologic first principles; by sign-posting relevant data arising from other patient groups with shared issues; to illustrate how recent scientific advances are (or should be) altering clinician perceptions of pubertal delay; and finally, to emphasise that the management of men and women presenting in advanced adult life with absent puberty cannot simply be extrapolated from paediatric practice. There is a broad spectrum of pubertal timing that varies among different populations, separated in time and space. Delayed puberty usually represents an extreme of the normal, a developmental pattern referred to as constitutional delay of growth and puberty (CDGP), but organic defects of the hypothalamo–pituitary–gonadal axis predisposing to hypogonadism may not always be initially distinguishable from it. CDGP and organic, or congenital hypogonadotrophic hypogonadism are both significantly more common in boys than girls. Moreover, around 1/3 of adults with organic hypogonadotrophic hypogonadism had evidence of partial puberty at presentation and, confusingly, some 5–10% of these subsequently may exhibit recovery of endogenous gonadotrophin secretion, including men with Kallmann syndrome. However, the distinction is crucial as expectative (‘watch-and-wait’) management is inappropriate in the context of hypogonadism. The probability of pubertal delay being caused by organic hypogonadism rises exponentially both with increasing age at presentation and the presence of associated ‘red flag’ clinical features. These ‘red flags’ comprise findings indicating lack of prior ‘mini-puberty’ (such as cryptorchidism or micropenis), or the presence of non-reproductive congenital defects known to be associated with specific hypogonadal syndromes, e.g. anosmia, deafness, mirror movements, renal agenesis, dental/digital anomalies, clefting or coloboma would be compatible with Kallmann (or perhaps CHARGE) syndrome. In children, interventions (whether in the form or treatment or simple reassurance) have been historically directed at maximising height potential and minimising psychosocial morbidity, though issues of future fertility and bone density potential are now increasingly ‘in the mix’. Apubertal adults almost invariably harbour organic hypogonadism, requiring sensitive acknowledgement of underlying personal issues and the timely introduction of sex hormone replacement therapy at more physiological doses.

Introduction: Turner syndrome is characterized by the absence, total or partial, of one X chromosome in females, being one of the most frequent chromosomal abnormalities. Diagnosis is made by karyotype. Turner syndrome manifestations include primary hypogonadism, before or after puberty (gonadal dysgenesis). The degree and extent of gonadal disfunction are variable.Objectives: We intended to assess clinical, karyotype, gonadal function and pelvic ultrasound characteristics in women with Turner syndrome.Material and Methods: Retrospective study of patients with Turner syndrome followed in Endocrinology and Human Reproduction Departments of Hospitais da Universidade de Coimbra - Centro Hospitalar e Universitário de Coimbra, E.P.E. We evaluated the entire sample and considered group 1 (with spontaneous puberty and menarche) and group 2 (without spontaneous puberty). Parameters assessed: age at initial study, puberty (Tanner stages), karyotype, FSH, pelvic ultrasound (initial and after puberty), diagnostic laparoscopy and pubertal induction. Statistical Program: SPSS (20.0).Results: Global sample: 79 patients, 14.7 ± 6.6 years. No pubertal signs in 57.1%; 67.1% with primary amenorrhea and 6.6% with secondary amenorrhea. Karyotype: X monosomy-37.2%, mosaicism-37.2%, X structural changes-25.6%. Median FSH of 59.5 mIU/ mL. Initial ultrasound: normal uterus 34.2%, atrophic uterus 65.8%; normal ovaries 21.6%, atrophic ovaries 78.4%, ovarian follicles in 5.1%. Post-puberty ultrasound: normal uterus 67.9%, atrophic uterus 32.1%; normal ovaries 36.4%, atrophic ovaries 63.6%. Laparoscopy was performed in 16 (20.3%) patients, confirming the sonographic findings. Only two women with induced puberty became pregnant: one spontaneously, interrupted; another by donated oocytes, normal outcome. Group 1 (with spontaneous puberty and menarche):20 (25.3%) patients, 16.1 ± 8.9 years. Tanner at baseline: M1-22.2%, M2-33.3%, M3-16.7%, M4-16.7%, M5-11.1%. Karyotype: mosaicism-65%, X structural changes-20%, X monosomy-15%. Median FSH of 7 mUI/mL. Initial ultrasound: normal uterus-72.2%,atrophic uterus 27.8%; normal ovaries 63.2%, atrophic ovaries 36.8%. Post-puberty ultrasound: normal uterus 100%; normal ovaries 72.7%, atrophic ovaries 27.3%. Group 2 (without spontaneous puberty): 59 (74.7%) patients, 14.0 ± 5.5 years. Tanner at baseline: M1-69.2%, M2-13.5%, M3-5.8%, M4-3.8%, M5-7.7%. Karyotype: X monosomy-43.9%, X structural changes-28.1% mosaicism-28.1%. Median FSH of 74 mUI/mL. Initial ultrasound: normal uterus 20.4%, atrophic uterus 79.6%; normal ovaries 7.4%, atrophic ovaries92.6%. Post-puberty ultrasound: normal uterus 60.0%, atrophic uterus 40.0%; normal ovaries 27.3%, atrophic ovaries 72.7%. Pubertal induction at 16.1 ± 4.1 years, with bone age of 12.7 ± 1.6 years. Groups 1 and 2 differ significantly in karyotype (p = 0.010), median FSH (p < 0.001), and uterine and ovarian dimensions (p < 0.001).Conclusions: Most patients had gonadal dysfunction and needed pubertal induction. Spontaneous puberty with menarche occurred in 25.3% of patients (predominantly mosaics). 43.9% of patients with pubertal induction had X monosomy. These patients fertility is compromised and, in some cases, we should refer to assisted reproductive specialist for pregnancy or fertility preservation.

Abstract Context: Pediatric management of patients with Turner syndrome focuses on height, frequently resulting in a delay of pubertal induction. The influence of pubertal management on psychosocial adjustment and sex life has not been evaluated in Turner syndrome patients. Objective: The objective of the study was to identify the determinants of self-esteem, social adjustment, and initiation of sex life in patients with Turner syndrome, particularly those related to pubertal management. Design: This was a prospective evaluation, the StaTur study. Setting: The study was conducted with a population-based registry of GH-treated patients. Participants: Participants included 566 young adult women with Turner syndrome, aged 22.6 ± 2.6 yr (range, 18.3–31.2). Main Outcome Measures: Measures used in the study were Coopersmith’s Self-Esteem Inventory, Social Adjustment Scale Self-Report, questions on sexual experience, and extensive data on pediatric management. Results: Low self-esteem was associated with otological involvement and limited sexual experience. Low social adjustment was associated with lower paternal socioeconomic class and an absence of sexual experience. Late age at first kiss or date was associated with cardiac involvement and a lack of spontaneous pubertal development. Age at first sexual intercourse was related to age at puberty and paternal socioeconomic class. Delayed induction of puberty had a long-lasting effect on sex life. Height and height gain due to GH treatment had no effect on outcomes. Conclusions: Puberty should be induced at a physiologically appropriate age in patients with Turner syndrome to optimize self-esteem, social adjustment, and initiation of the patient’s sex life. Therapeutic interventions altering normal pubertal development in other groups of patients should be reconsidered in light of these findings.

Abstract Female congenital hypogonadotropic hypogonadism (CHH) is a rare condition, with a strong genetic background, characterized by absent or incomplete pubertal development, for which inductive treatment with sex-hormone is required. Although the available data, mostly coming from studies in patients with Turner syndrome, indicate transdermal estradiol (TDE) as the first-choice formulation, no internationally validated therapeutic schemes are currently available. Furthermore, data on CHH patients are certainly lacking and there is no standard of care for pubertal induction in this specific population. The aim of our work was the retrospective analysis of the data from a collection of case reports of pubertal induction in CHH patients referred to our Center. Six patients underwent induction with transdermal estradiol (TDE) at the starting dose of 0.1µg/kg/day (night-time for the first 4-6 months), increased every 4-6 months up to the adult dose, for a mean period of 2.86 ± 0.45 ys. Micronized progesterone (200 mcg) was introduced at reaching of 50µg dose or if breakthrough bleeding occurred. Treatment was monitored through clinical and anthropometric evaluations at each dose modification. The average age of induction was 17.25 ± 1.41 ys, with each bone age&gt; 13 ys. Three out of six patients already had a Tanner B2 stage at diagnosis. The mean times of pubertal advancement were respectively 1.3 ± 0.46 ys for the achievement of B3, 2.13 ± 0.29 ys for the B4 and 2.35 ± 0.77 ys for menarche; all the patients reached an adult breast conformation (B5) in 2.81 ± 0.28 ys. These data are consistent with physiological pubertal progress. All of them achieved adequate uterine development (medium longitudinal diameter 72.2 ± 3.37mm), except one patient with suboptimal development (54mm). The final height (FH) was adequate in all patients, with SDS FH +1.6 (-0.43 - +3.38), in spite of an average growth of 4.11 cm (2.5-6) ​​during the induction period and a growth rate &gt; 2cm/year only in 50% of patients. No side effects were reported, and individual compliance and satisfaction were quite high. This clinical experience suggests that the adopted regimen, consistent with current literature, guarantees excellent efficacy and safety. However, further studies are needed to identify the optimal treatment in adolescents with CHH, taking into account their higher age at the start of induction, the modest impact on growth and final stature, to focus on the specific clinical objectives in these patients

A single injection of 400 i.μ. pregnant mare's serum gonadotrophin (PMSG) plus 200 i.μ. human chorionic gonadotrophin (HCG) has been shown to induce puberty in a high proportion of gilts treated (Burnett and Walker, 198S). However, studies indicate that the hormone treatment may fail to initiate normal oestrous cycling after the pubertal ovulation. The work of Paterson and Lindsay (1981) has shown that housing gilts in contact with boars throughout the cycle after puberty induction will enhance the proportion of animals which maintain cyclic activity to a second ovulation. The purpose of the experiment reported here was to examine the effect of boar contact and the timing of the introduction of boar contact on the maintenance of cyclic activity after puberty induction by PMSG + HCG.

Abstract This study aimed to determine if heifers induced to puberty had damage in reproductive performance compared with heifers that reach puberty naturally. Nellore heifers (n = 210) were weaned at 8 ± 0.7 mo of age were assigned to 42 feedlot pens according to BW (184 ± 1 kg). The diet was compounded by Tifton-85 haylage (18% CP; 55% TDN) ad libitum and supplement (4g/kg of BW; 25% CP; 60% TDN). Puberty and growth were assessed weekly. At 14 mo of age, 46 heifers reached puberty naturally (precocious heifers; PH) and 164 non-pubertal heifers were submitted to puberty induction with progesterone (P4) insert for 10 days and estradiol cypionate (0.5 mg) at P4 removal (puberty induction; PI). After fourteen days, all heifers were submitted to TAI. Heifers were considered pregnant at 20 days (P20) after AI when CL had blood flow &lt; 25% of area (Power-Doppler). Pregnancy rate was also determined at 30 (P30) and 60 (P60) days after AI by embryo detection. Early (P20 – P30) and late (P30 – P60) embryonic loss were determined. Reproductive data were analyzed by GLIMMIX, and BW was analyzed using repeated measures over time (MIXED; SAS 9.3). The PH was heavier than PI from 8 to 16 mo of age, which BW was 296 and 285 ± 3 kg at 14 mo of age, respectively. At beginning of TAI, 88% of PI heifers had a CL. Pregnancy rate was similar (P &gt; 0.05) between treatments, in which pregnancy rate at 20, 30 or 60 days after AI was 65, 47 and 43% for PH and 61, 53 and 48% for PI, respectively. Early (26 vs 14%) and late (9 vs 9%) embryonic loss were similar (P &gt; 0.05) in PH and PI, respectively. In summary, natural or induced pubertal heifers had similar reproductive performance.

Background Delayed puberty is a possible complication of Epidermolysis Bullosa (EB), though the actual incidence is still unknown. In chronic illnesses delayed puberty should be correctly managed since, if untreated, can have detrimental effects on adult height attainment, peak bone mass achievement and psychological health. Aims and methods This is a single-centre study on pubertal development, growth and bone status in EB. Auxological, densitometric (areal Bone Mineral Density-aBMD Z-score, Bone Mineral Apparent Density-BMAD Z-score, Trabecular Bone Score-TBS and Bone Strain Index-BSI at Lumbar spine) and body composition data (Total Body DXA scans) were collected. Disease severity was defined according to Birmingham Epidermolysis Bullosa Severity (BEBS) score. Results Twenty-one patients (12 Recessive Dystrophic EB-RDEB, 3 Dominant Dystrophic EB, 3 Junctional EB-JEB, 2 EB Simplex and one Kindler EB) aged 13 years (females) or 14 years (males) and above were enrolled (age 16.2±2.5 years, M/F 11/10). Short stature was highly prevalent (57%, mean height -2.12±2.05 SDS) with 55% patients with height <-2SD their mid-parental height. 7/21 patients (33%, 6 RDEB and 1 JEB) had delayed puberty with a median BEBS of 50 (range 29 to 63), a height SDS of -2.59 SDS (range -5.95 to -2.22) and a median lumbar BMAD Z-score of -4.0 SDS (range -5.42 to -0.63 SDS). Pubertal status was negatively associated with BEBS, skin involvement, inflammatory state and positively with height SDS and BMI SDS. Conclusions Pubertal delay is highly prevalent in EB, especially in patients with RDEB and JEB, high severity score and inflammatory state. Moreover, pubertal delay worsens growth impairment and bone health. A study on pubertal induction is ongoing to enlighten possible beneficial effects on adult height attainment and peak bone mass accrual.

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17β-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions.

Background: La terapia sostitutiva estroprogestinica ai fini dell’induzione puberale nelle pazienti affette da ipogonadismo è volta a mimare i fisiologici cambiamenti che avvengono durante la pubertà. Tuttavia, al momento in letteratura non vi è ancora una consensus sul migliore schema terapeutico da utilizzare, tale da essere al contempo fisiologico ed efficace. In particolare, i dati presenti in letteratura mostrano come più della metà delle pazienti affette da ipogonadismo presenti un’insufficiente maturazione uterina al termine dell’induzione, elemento in gran parte responsabile degli insoddisfacenti outcome di concepimento di questa categoria di pazienti. Scopo: Analizzare longitudinalmente dati di induzione puberale in pazienti affette da ipogonadismo ipogonadotropo o insufficienza ovarica primitiva da qualsiasi causa (congenita, acquisita, isolata o associata ad altri deficit ipofisari, nell’ambito della Sindrome di Turner o secondaria a chemoterapici gonadotossici) con particolare attenzione agli outcomes auxologici e allo sviluppo uterino, in relazione alle sottostanti differenti categorie diagnostiche e ai diversi schemi utilizzati. Pazienti e Metodi: A questo scopo, nell’impossibilità di creare studi randomizzati controllati, in assenza di preparati estrogenici specificamente approvati per la popolazione pediatrica, è stato creato un registro multicentrico. Delle 106 ragazze affette da ipogonadismo (di età superiore a 11 anni e con stadio Tanner≤2) che hanno ricevuto terapia estroprogestinica allo scopo di induzione puberale incluse nel registro, abbiamo considerato 95 pazienti (età media 13.5 anni) trattate con 17β-estradiolo in formulazione transdermica (TD) per almeno un anno (mediana di trattamento 3.3 anni). L'induzione è stata iniziata con una dose mediana di 17β-estradiolo TD di 0.14 mcg/kg/die, con graduali incrementi a cadenza semestrale. I dati auxologici, biochimici (livelli di estradiolo) e radiologici (ecografia pelvica) sono stati raccolti al basale e durante il follow-up. In 61/95 ragazze, il progesterone è stato introdotto dopo un intervallo mediano di 2.2 anni. L'induzione è stata considerata completata per le 49/95 pazienti che avevano iniziato una terapia contraccettiva orale combinata (COC) o introdotto il progestinico ad un concomitante dosaggio di 17β-estradiolo TD di almeno 50 mcg/die o 1 mcg/kg/die. Risultati: Al termine dell’induzione, il 90.0% delle pazienti aveva raggiunto lo stadio Tanner IV ed il 41.0% lo stadio V. In particolare, il raggiungimento dell’ultimo stadio di Tanner (Tanner V) è risultato positivamente associato alla dose di 17β-estradiolo all’introduzione del progestinico (P=0.034). Il diametro longitudinale uterino ha mostrato un graduale aumento durante la terapia estrogenica ed è risultato significativamente correlato alla dose di 17β-estradiolo in ogni momento dell’induzione (P<0.0001). Tuttavia, il diametro longitudinale finale è risultato superiore a 65 mm in soli 17/45 pazienti (38%). Alla regressione lineare, la presenza di un’anamnesi positiva per pregressa irradiazione pelvica è risultata il maggior determinante l’insufficiente maturazione uterina (P=0.034). Dopo correzione per irradiazione pelvica, il diametro longitudinale uterino è risultato associato alla dose di 17β-estradiolo all’introduzione del progestinico (P=0.043). Inoltre, il diametro uterino longitudinale finale non si è mostrato significativamente differente da quello valutato dopo almeno sei mesi dall’introduzione della terapia COC. Conclusioni: L’analisi della presente coorte di pazienti affette da ipogonadismo, ha messo in luce come il raggiungimento degli obiettivi terapeutici debba essere individualizzato e contestualizzato in relazione alla patologia di base. Il periodo adolescenziale rappresenta, per tutte le ragazze, una finestra temporale fondamentale ai fini del raggiungimento di una corretta maturazione uterina e mammaria. Pertanto, data l’evidenza di come l’introduzione del progestinico impedisca qualsiasi successiva variazione in termini di volume uterino e porti al mancato raggiungimento dell’ultimo stadio di Tanner, tale terapia dovrebbe essere introdotta solo in presenza di un’adeguata dose estrogenica e di un’appropriata risposta clinica (uterina e mammaria). La prosecuzione della raccolta dei dati attraverso il registro permetterà di confermare tali risultati su larga scala, al fine di individuare lo schema terapeutico migliore in ogni specifica categoria di pazienti, in particolare nella delicata popolazione delle ragazze “cancer survivors”.
Background: Pubertal induction in girls with hypogonadism through estrogen replacement therapy (ERT) aims at mimicking physiological puberty. To date, the best induction regimen, being physiological and effective at the same time, is still to be established. Moreover, available data in the literature show a poor uterine development at the end of the induction in more than a half hypogonadal patients: this probably represents one of the most important contributing factors for negative pregnancy outcomes of this specific population. Aims: We analysed longitudinal data on pubertal induction in girls with hypogonadotropic hypogonadism or primary ovarian insufficiency (congenital, acquired, isolated or associated with multiple pituitary hormone deficiencies, either associated with Turner Syndrome or secondary to late effects of cancer treatment) in order to insight into auxological and uterine outcomes in the light of different underlying diagnosis and regimens used. Methods: Due to the lack of licensed specific hormone preparations for pubertal induction, randomized-controlled trials are not feasible; thus, a multicentre clinical registry was created. Out of 106 hypogonadal girls (chronological age>10.9 years, Tanner stage≤2) who received ERT for pubertal induction, we considered 95 girls (median age 13.5 years) treated with transdermal (TD) 17β-estradiol patches for at least one year (median 3.3 years). Induction was started at a median dose of 0.14 mcg/kg/day TD 17β-estradiol, with a six-monthly increase. Auxological, biochemical (estradiol levels) and radiological (pelvic US) data were collected at baseline and during follow-up. In 61/95 girls, progesterone was introduced after a median of 2.2 years. Induction was considered completed for the 49/95 patients who were started on combined oral contraceptive (COC) or progesterone plus at least 50 mcg/day or 1 mcg/kg/day of TD 17β-estradiol. Results: At the end of induction, 90.0% patients had achieved Tanner stage IV and 41.0% Tanner stage V, the latter being associated with 17β-estradiol dose at progesterone introduction (P=0.034). Uterine longitudinal diameter (ULD) showed a gradual increase during ERT and a significant correlation with 17β-estradiol dosage (P<0.0001) at any point of induction. Nonetheless, the final ULD was>65 mm in only 17/45 (38%). At multiple regression analysis, a history of pelvic irradiation represented the major determinant of reduced final ULD (P=0.034). After correction for uterine irradiation, ULD was associated with 17β-estradiol dose at progesterone introduction (P=0.043). Final ULD was not significantly different from the one assed after COC introduction. Conclusions: Our results show that therapeutic goals should be individualized and tailored to the underlying different diagnostic categories. Moreover, adolescence represents a critical window for uterine and breast development: indeed, given the evidence that progestins may hamper the subsequent changes in uterus volume or the achievement of the last Tanner stage, such therapy should be started only in the presence of a concomitant adequate ERT dose and an appropriate clinical response (uterus and breast development). At present, data collection is ongoing to confirm these assumptions on a larger scale and to identify the best induction regimen for each diagnostic category, with particular focus on the specific needs of childhood cancer survivors.

Titulo retirado da capa
Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, São José dos Pinhais, 2012
Bibliografia: f. 62-64
O presente estudo objetivou verificar a influência do protocolo hormonal com três manejos, utilizando a progesterona intravaginal de uso único, em novilhas pré-púberes e púberes, visando a inseminação artificial em tempo fixo (IATF). Foram utilizadas 447
The present study aim to verify the influence of using hormone in tree handle protocol which use progesterone intra vaginal inserts in pre pubertal and pubertal beef heifers, in purpose to achieve a pre timed A.I. 447 cross breed heifers ( Nelore X Red An

Chez les rongeurs, les facteurs sociaux sont connus pour pouvoir moduler la transition pubertaire. Ainsi une jeune souris femelle mise en contact avec un mâle adulte présentera une ouverture vaginale plus précoce qu’une femelle isolée du mâle. L’objectif de ma thèse a été de caractériser les conséquences d’une exposition précoce au mâle dans l’espèce caprine. Les caprins sont une espèce dont la reproduction est saisonnée et permettant, de par sa taille, une étude plus fine des sécrétions endocrines que les rongeurs. Nos résultats ont permis de mettre en évidence que la présence de boucs sexuellement actifs induit une puberté précoce chez les chevrettes, l’ovulation pouvant être induite dès l’âge de 3 mois et demi. Les femelles présentent suite à cette première ovulation une cyclicité régulière ainsi qu’une maturation précoce du tractus génital. Le niveau d’activité sexuelle du bouc est un facteur crucial à l’induction d’une puberté précoce chez la chèvre puisque la présence de mâles castrés n’a aucun effet et que les femelles sont toutes pubères dans le mois suivant l’entrée en saison sexuelle des mâles. Ce travail démontre, dans l’espèce caprine, un rôle crucial de l’environnement social dans la régulation de la maturation sexuelle. Plus particulièrement, cela met en évidence que la présence de boucs peut réactiver efficacement et de manière très précoce l’axe gonadotrope de jeunes chèvres immatures
In rodents, social factors are known to modulate the pubertal transition. Hence, young female mice exposed to adult male exhibit an earlier vaginal opening than young females isolated from male. The aim of my thesis was to characterize the consequences of a precocious exposure to male in another specie, goats. Goats are seasonal breeders and due to their size the fine study of endocrine secretions is easier than in rodents. Our results highlighted that an early exposure to sexually active bucks induces a precocious puberty in young female goats. The first ovulation can be induced as early as 3.5 months old, following this induced first ovulation, goats remain cycling regularly. Females precociously exposed to bucks also exhibit an acceleration of the genital tract maturation. The level of sexual activity of the male is a crucial criteria to induce a precocious puberty in goats as exposure to castrated bucks had no effect on the age at puberty. Moreover, all females exposed to intact bucks ovulated for the first time within a month after buck started to exhibit sexual behaviors. This work revealed, in goats, a crucial role of the social environment on the regulation of sexual maturation. More precisely, it highlights that exposure to bucks is highly efficient to reactivate precociously the gonadotrope axis of youg immature goats

Thesis (M.S.)--West Virginia University, 2002.
Title from document title page. Document formatted into pages; contains vi, 63 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 49-62).

In dieser retrospektiven klinischen Studie wurden die Akten von 89 Patientinnen mit Ullrich-Turner-Syndrom ausgewertet, die zwischen 1974 und 2004 in der Universitätsklinik und Poliklinik für Kinder und Jugendliche in Leipzig behandelt worden sind. Berücksichtigt wurde die Verteilung der Karyotypen im Patientenkollektiv sowie das Auftreten von assoziierten Begleiterkrankungen. Das Alter bei Diagnosestellung, die Größe bei Diagnosestellung und die Gründe für die Verdachtsdiagnose Ullrich-Turner-Syndrom wurden analysiert. Darüber hinaus untersuchte der Autor die durchgeführten Maßnahmen zur Pubertätsinduktion im Hinblick auf ihren Beginn und Erfolg sowie deren Einfluss auf die Wachstumraten. Gut 50% der Patientinnen besaßen den Karyotyp 45,X, die anderen Karyotypen setzten sich aus Mosaiken zusammen. Assoziierte Begleiterkrankungen waren im Patientenkollektiv unterrepräsentiert. Das durchschnittliche Alter bei Diagnosestellung betrug 8,21 Jahre, es fiel während des Beobachtungszeitraumes signifikant ab. Der durchschnittliche Größen-SDS zum Zeitpunkt der Diagnosestellung betrug -2,86. Es wurde, verglichen mit den Empfehlungen der Leitlinien, eine verspätete Diagnosestellung konstatiert. Die Pubertätsinduktion begann mit durchschnittlich 13,93 Jahren mit einer signifikanten Reduktion im Verlauf. Die Dauer vom Beginn der Pubertätsinduktion bis zum Eintreten der Menarche betrug 2,51 Jahre, die Dauer vom Tannerstadium B2 zum Stadium B5 betrug gut 27 Monate. Eine Menarche wurde bei nur 65% der Patientinnen sicher beobachtet. Die Ergebnisse wurden kritisch überprüft und in den Kontext anderer Studien eingeordnet. Aus den Ergebnissen wurde gefolgert, dass das Ullrich-Turner-Syndrom, trotz einer positiven Entwicklung in den letzten Jahren, noch immer zu spät diagnostiziert wurde. Die Pubertätsinduktion verlief trotz der verzögerten Diagnosestellung hinsichtlich der Entwicklung der Tannerstadien erfolgreich. Demgegenüber blieb die Induktion der Menarche nur mäßig erfolgreich. Eine Beeinflussung der Wachstumraten durch die Östrogentherapie wurde nicht beobachtet.

In dieser retrospektiven klinischen Studie wurden die Akten von 89 Patientinnen mit Ullrich-Turner-Syndrom ausgewertet, die zwischen 1974 und 2004 in der Universitätsklinik und Poliklinik für Kinder und Jugendliche in Leipzig behandelt worden sind. Berücksichtigt wurde die Verteilung der Karyotypen im Patientenkollektiv sowie das Auftreten von assoziierten Begleiterkrankungen. Das Alter bei Diagnosestellung, die Größe bei Diagnosestellung und die Gründe für die Verdachtsdiagnose Ullrich-Turner-Syndrom wurden analysiert. Darüber hinaus untersuchte der Autor die durchgeführten Maßnahmen zur Pubertätsinduktion im Hinblick auf ihren Beginn und Erfolg sowie deren Einfluss auf die Wachstumraten. Gut 50% der Patientinnen besaßen den Karyotyp 45,X, die anderen Karyotypen setzten sich aus Mosaiken zusammen. Assoziierte Begleiterkrankungen waren im Patientenkollektiv unterrepräsentiert. Das durchschnittliche Alter bei Diagnosestellung betrug 8,21 Jahre, es fiel während des Beobachtungszeitraumes signifikant ab. Der durchschnittliche Größen-SDS zum Zeitpunkt der Diagnosestellung betrug -2,86. Es wurde, verglichen mit den Empfehlungen der Leitlinien, eine verspätete Diagnosestellung konstatiert. Die Pubertätsinduktion begann mit durchschnittlich 13,93 Jahren mit einer signifikanten Reduktion im Verlauf. Die Dauer vom Beginn der Pubertätsinduktion bis zum Eintreten der Menarche betrug 2,51 Jahre, die Dauer vom Tannerstadium B2 zum Stadium B5 betrug gut 27 Monate. Eine Menarche wurde bei nur 65% der Patientinnen sicher beobachtet. Die Ergebnisse wurden kritisch überprüft und in den Kontext anderer Studien eingeordnet. Aus den Ergebnissen wurde gefolgert, dass das Ullrich-Turner-Syndrom, trotz einer positiven Entwicklung in den letzten Jahren, noch immer zu spät diagnostiziert wurde. Die Pubertätsinduktion verlief trotz der verzögerten Diagnosestellung hinsichtlich der Entwicklung der Tannerstadien erfolgreich. Demgegenüber blieb die Induktion der Menarche nur mäßig erfolgreich. Eine Beeinflussung der Wachstumraten durch die Östrogentherapie wurde nicht beobachtet.

Transgender adolescent healthcare is a relatively novel part of endocrine medicine. Treatment protocols have emerged since the late1990’s and outcome data have become available more recently. A multidisciplinary approach with psychology and endocrinology is required to accommodate the specific needs of developing transgender adolescents and their primary caretakers. Therefore, treatment is ideally provided by specialized centres. However, with a growing population in numbers, all physicians should be familiar with treatment protocols. The endocrine treatment of transgender youth differs from that of transgender adults. The first step of treatment is a phase of gonadal suppression using either gonadotropin hormone-releasing hormone analogues (GnRHa) or, alternatively, progestogens, or antiandrogens. Second step is the induction of sexual characteristics of the affirmed gender using synthetic sex steroids in increasing dosages to mimic a pubertal fase. These specific therapeutics approaches of the transgender adolescent are outlined in this chapter.

Cancer is the consequence of the recalcitrant multiplication of the transformed cells. Cancer cells grow and proliferate at a fast pace and do not follow normal regulation of cell division. Breast cancer is a heterogeneous group of diseases, which is the second leading cause of death among women. Although androgen is primarily considered a male steroid hormone, it also has an important role in the female reproductive system. The literature evidence suggests the role of androgen receptors (AR) in the normal development of the breast. At puberty, the expression of AR is even more than ER, suggesting its importance during the process of sexual development; its activity maintains the ER-induced cell proliferation and normal development of the breast. Epidemiological studies have suggested a positive correlation between high endogenous androgens and the risk of breast cancer in both pre- and postmenopausal women. In both ER and PR-positive breast cancers, AR is expressed in 60-70% of the cases. AR is also reported to be co-expressed with ER in around 80-90% of breast cancer cases and is considered an independent prognostic factor of ER-positive breast cancers. Tumor-microenvironment has a complex role in tumor initiation, progression, and metastasis. Tumor-infiltrating and resident cells secretes a variety of inflammatory and anti-inflammatory cytokines, which in turn either inhibit or promote tumor growth. Immunosuppressive and immuno-inductive effects of androgen have been reported in various studies. Androgens have been reported to influence the adaptive immune system more than the innate immune system in many ways. Crosstalk of androgen and cytokine signaling has many effects in breast cancer epidemiology. So, in this chapter, we will discuss the various immune-endocrine perspectives of breast cancers.

Case Report: 19 yr old unmarried girl c/o abdominal distension, loss of appetite and Irregular menstrual cycles x 5 months. USG: gross ascites, liver, Lobulated isoechoic mass in right adnexa, 7x5 cm, abutting right ovary. CA125: 1297 U/ml. FNAC Degenerated crushed cells & stromal fragments. Few scattered benign oval/spindle cells. Laparoscopy f/b laparotomy: 6 litres of straw colored asciic fluid drained. Uterus, left adnexa normal. Rt ovarian mass 6x7 cm, bilobed, arising from ovary. Solid, stuck in POD Adherent to gut. Right oophrectomy done. CA-125: 22 u/ml on day 6 post op. HPE – Sclerosing stromal tumor. Discussion: Sclerosing sex cord stromal tumour of the ovary is a rare tumor; accounts for 6% of ovarian stromal tumors Over a 100 reported tumors in literature. 80% of SST seen in second and third decade of life. Essentially a benign tumour, Usually a unilateral nonfunctioning tumor. Few cases with elevated serum CA-125 and hormonal abnormalities have been reported. Endocrine alterations caused by secretion of estrogen, progesterone or testosterone; induction of precocious puberty. Conclusion: Unilateral oophrectomy is the treatment. No recurrence of the tumor in the patients treated by oophorectomy or by conservative resection of the tumor. Excision of the tumor isfollowed by normal menses, pregnancy has also been reported.

Both the genes and cDNA sequences encoding the b-subunits of black carp LH and FSH were isolated, cloned and sequenced. Sequence analysis of the bcFSHb and LHb5'flanking regions revealed that the promoter region of both genes contains canonical TATA sequences, 30 bp and 17 bp upstream of the transcription start site of FSHb and LHb genes, respectively. In addition, they include several sequences of cis-acting motifs, required for inducible and tissue-specific transcriptional regulation: the gonadotropin-specific element (GSE), GnRH responsive element (GRE), half sites of estrogen and androgen response elements, cAMP response element, and AP1. Several methods have been employed by the Israeli team to purify the recombinant b subunits (EtOH precipitation, gel filtration and lentil lectin). While the final objective to produce pure recombinantGtH subunits has not yet been achieved, we have covered much ground towards this goal. The black carp ovary showed a gradual increase in both mass and oocyte diameter. First postvitellogenic oocytes were found in 5 yr old fish. At this age, the testes already contained spermatozoa. The circulating LH levels increased from 0.5 ng/ml in 4 yr old fish to >5ng/ml in 5 yr old fish. In vivo challenge experiments in black carp showed the initial LH response of the pituitary to GnRH in 4 yr old fish. The response was further augmented in 5 yr old fish. The increase in estradiol level in response to gonadotropic stimulation was first noted in 4 yr old fish but this response was much stronger in the following year. In vivo experiments on the FSHb and LHb mRNA levels in response to GnRH were carried out on common carp as a model for synchronom spawning cyprinids. These experiments showed the prevalence of FSHP in maturing fish while LHP mRNA was prevalent in mature fish, especially in females. The gonadal fat-pad was found to originate from the retroperitoneal mesoderm and not from the genital ridge, thus differing from that reported in certain amphibians This tissue possibly serves as the major source of sex steroids in the immature black carp. However, such a function is taken over by the developing gonads in 4 yr old fish. In the striped bass, we described the ontogeny of the neuro-endocrine parameters along the brain-pituitary-gonadal axis during the first four years of life, throughout gonadal development and the onset of puberty. We also described the responsiveness of the reproductive axis to long-term hormonal manipulations at various stages of gonadal development. Most males reached complete sexual maturity during the first year of life. Puberty was initiated during the third year of life in most females, but this first reproductive cycle did not lead to the acquisition of full sexual maturity. This finding indicates that more than one reproductive cycle may be required before adulthood is reached. Out of the three native GnRHs present in striped bass, only sbGnRH and cGnRH II increased concomitantly with the progress of gonadal development and the onset of puberty. This finding, together with data on GtH synthesis and release, suggests that while sbGnRH and cGnRH II may be involved in the regulation of puberty in striped bass, these neuropeptides are not limiting factors to the onset of puberty. Plasma LH levels remained low in all fish, suggesting that LH plays only a minor role in early gonadal development. This hypothesis was further supported by the finding that experimentally elevated plasma LH levels did not result in the induction of complete ovarian and testicular development. The acquisition of complete puberty in 4 yr old females was associated with a rise in the mRNA levels of all GtH subunit genes, including a 218-fold increase in the mRNA levels of bFSH. mRNA levels of the a and PLH subunits increased only 11- and 8-fold, respectively. Although data on plasma FSH levels are unavailable, the dramatic increase in bFSH mRNA suggests a pivotal role for this hormone in regulating the onset and completion of puberty in striped bass. The hormonal regulation of the onset of puberty and of GtH synthesis and release was studied by chronic administration of testosterone (T) and/or an analog of gonadotropin-releasing hormone (G). Sustained administration of T+G increased the mRNA levels of the PLH subunit to the values characteristic of sexually mature fish, and also increased the plasma levels of LH. However, these changes did not result in the acceleration of sexual maturation. The mRNA levels of the bFSH subunit were slightly stimulated, but remained about 1/10 of the values characteristic of sexually mature fish. It is concluded that the stimulation of FSH gene expression and release does not lead to the acceleration of sexual maturity, and that the failure to sufficiently stimulate the bFSH subunit gene expression may underlie the inability of the treatments to advance sexual maturity. Consequently, FSH is suggested to be the key hormone to the initiation and completion of puberty in striped bass. Future efforts to induce precocious puberty in striped bass should focus on understanding the regulation of FSH synthesis and release and on developing technologies to induce these processes. Definite formulation of hormonal manipulation to advance puberty in the striped bass and the black carp seems to be premature at this stage. However, the project has already yielded a great number of experimental tools of DNA technology, slow-release systems and endocrine information on the process of puberty. These systems and certain protocols have been already utilized successfully to advance maturation in other fish (e.g. grey mullet) and will form a base for further study on fish puberty.