Long-Term Suppression of Pituitary-Gonadal Function with Three-Month Depot of Leuprorelin Acetate in a Girl with Central Precocious Puberty

Schroeter, Manuela; Baus, Inka; Sippell, Wolfgang G.; Partsch, Carl-Joachim

doi:10.1159/000066445

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…The experimental arrest of puberty in the two Luprontreated groups is consistent with the clinical use of Lupron and other GnRH analogues in the treatment of precocious puberty [42,43]. Importantly, the data show that blocking the action of endogenous GnRH by the analogue does not hinder neuroendocrine development, as morning and evening LH were increased by 4 wk following termination of treatment and perineal swelling and menarche occurred, on the average, within 2 mo of ending the Lupron treatments, a situation analogous to girls coming off of Lupron therapy for precocious puberty [44].…”

Section: Con (N ϭ 7)supporting

confidence: 75%

Reduced Growth Hormone Secretion Prolongs Puberty But Does Not Delay the Developmental Increase in Luteinizing Hormone in the Absence of Gonadal Negative Feedback1

Wilson

Chikazawa

Fisher

et al. 2004

Biology of Reproduction

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Previous studies have shown that the growth hormone (GH) axis is important for timing the later stages of puberty in female monkeys. However, it is not clear whether these growth-related signals are important for the initiation of puberty and early pubertal events. The present study, using female rhesus monkeys, used two approaches to answer this question. Experiment 1 tested the hypothesis that reduced GH secretion would blunt the rise in nocturnal LH secretion in young (17 mo; n = 7) but not older adolescent ovariectomized females (29 mo; n = 6). Reduced GH secretion was induced by treating females with the sustained release somatostatin analogue formulation, Sandostatin LAR (625 microg/kg). Morning (0900-0930 h) and evening (2200-2230 h) concentrations of bioactive LH were higher in older adolescent compared to young adolescent females. However, diurnal concentrations were not affected by the inhibition of GH secretion in either age group when compared to the placebo-treated, control condition. Experiment 2 tested the hypothesis that reduced GH secretion induced in young juvenile females would delay the initial increase in nocturnal LH secretion and subsequent early signs of puberty. In order to examine this hypothesis, puberty in control females (n = 7) was compared to those in which puberty had been experimentally arrested until a late adolescent age (29 mo) by the use of a depot GnRH analogue, Lupron (750 microg kg(-1) mo(-1); n = 7). Once the analogue treatment was discontinued, the progression of puberty was compared to a group treated in a similar fashion but made GH deficient by continuous treatment with Sandostatin LAR (n = 6). Puberty occurred as expected in control females with the initial rise in evening LH at 21 mo, menarche at 22 mo, and first ovulation at 30 mo. As expected, Lupron arrested reproductive maturation, but elevations in morning and evening LH and menarche occurred within 2 mo of the cessation of Lupron in both Lupron and Lupron-GH-suppressed females. In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo). These data indicate that within this experimental model, reduced GH secretion does not perturb the early stages of puberty but supports previous observations that the GH axis is important for timing the later stages of puberty and attainment of fertility. Taken together, the data indicate that factors that reduce GH secretion may have a deleterious effect on the completion of puberty.

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Section: Con (N ϭ 7)supporting

confidence: 75%

Reduced Growth Hormone Secretion Prolongs Puberty But Does Not Delay the Developmental Increase in Luteinizing Hormone in the Absence of Gonadal Negative Feedback1

Wilson

Chikazawa

Fisher

et al. 2004

Biology of Reproduction

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“…Further side effects include minor menopausal symptoms in girls (e.g. head ache, nausea, hot flushes in 2-5% of patients) and local allergic reactions in up to 10% of patients [135,141,142], as well as the formation of sterile abscesses at the injection site in both sexes [132,133,[156][157][158]. In our experience the risk of a sterile abscess increases with the injection dose and volume and is greater when injected in the abdomen than in the thigh.…”

Section: Side Effectsmentioning

confidence: 74%

“…In a couple of pilot studies the efficacy of this preparation for treating CPP has been successfully tested [141,142] and has now been licensed for CPP in France and Italy. From the children's point of view it would be desirable to make treatment more convenient by lengthening the injection intervals.…”

Section: Treatment Optionsmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Analogue Treatment for Precocious Puberty

Heger

Sippell

Partsch

2005

Endocrine Development

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Central precocious puberty (CPP) is the premature onset of puberty due to a precocious activation of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. This condition results in accelerated development of secondary sex characteristics, accelerated bone maturation, impaired final height with disproportioned body appearance and can have a disturbing impact on the psychosocial behavior of children suffering from CPP. It is therefore necessary to assess the hormonal status of children who show pubertal signs before the age 8 years in girls and 9 years in boys. The indication for treatment should be made after evaluating pubertal progression, progression of bone age maturation and final height prognosis, development of reproductive function, and psychosocial adjustment and well-being. This paper summarizes the experience of GnRH agonist treatment, which is momentarily the treatment of choice for central precocious puberty in children.

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“…40 Despite the fact that the intramuscular formulation is not FDA approved for subcutaneous injection, data are available suggesting that this route of administration is safe and effective. [41][42][43][44][45][46][47] However, adverse reactions including erythema, edema, urticaria, injection-site pain, sterile abscess, or ulceration at the injection site have been reported. Also, subcutaneous nodules or granulomas have been observed, and it is not known if this has any effect on drug absorption.…”

Section: Gonadotropin-releasing Hormone Analogsmentioning

confidence: 99%

Management of Menorrhagia Associated with Chemotherapy‐Induced Thrombocytopenia in Women with Hematologic Malignancy

2011

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Abnormal uterine bleeding in women with a blood dyscrasia, such as leukemia, or who experience thrombocytopenia secondary to myelosuppressive chemotherapy is a clinical condition associated with significant morbidity. Consequently, effective management is necessary to prevent adverse outcomes. Prevention of menorrhagia, defined as heavy regular menstrual cycles with more than 80 ml of blood loss/cycle or a cycle duration longer than 7 days, in this patient population is the goal of therapy. Gonadotropin-releasing hormone analogs (e.g., leuprolide) are promising therapies that have been shown to decrease vaginal bleeding during periods of thrombocytopenia and to have minimal adverse effects other than those associated with gonadal inhibition. In patients who experience menorrhagia despite preventive therapies, or in patients who have thrombocytopenia and menorrhagia at diagnosis, treatment is indicated. For these women, treatment options may include platelet transfusions, antifibrinolytic therapy (e.g., tranexamic acid), continuous high-dose oral contraceptives, cyclic progestins, or other therapies for more refractory patients such as danazol, desmopressin, and recombinant factor VIIa. Hormonal therapies are often the mainstay of therapy in women with menorrhagia secondary to thrombocytopenia, but data for these agents are sparse. The most robust data for the treatment of menorrhagia are for tranexamic acid. Most women receiving tranexamic acid in randomized trials experienced meaningful reductions in menstrual bleeding, and this translated into improved quality of life; however, these trials were not performed in patients with cancer. Further clinical trials are warranted to evaluate both preventive and therapeutic agents for menorrhagia in premenopausal women with cancer who are receiving myelosuppressive chemotherapy.

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Long-Term Suppression of Pituitary-Gonadal Function with Three-Month Depot of Leuprorelin Acetate in a Girl with Central Precocious Puberty

Cited by 5 publications

References 21 publications

Reduced Growth Hormone Secretion Prolongs Puberty But Does Not Delay the Developmental Increase in Luteinizing Hormone in the Absence of Gonadal Negative Feedback1

Reduced Growth Hormone Secretion Prolongs Puberty But Does Not Delay the Developmental Increase in Luteinizing Hormone in the Absence of Gonadal Negative Feedback1

Gonadotropin-Releasing Hormone Analogue Treatment for Precocious Puberty

Management of Menorrhagia Associated with Chemotherapy‐Induced Thrombocytopenia in Women with Hematologic Malignancy

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