Simulation of the Normal Menstrual Cycle in Kallman's Syndrome by Pulsatile Administration of Luteinizing Hormone-Releasing Hormone (Lhrh)

Crowley, William F.; McArthur, Janet W.

doi:10.1210/jcem-51-1-173

Cited by 293 publications

(95 citation statements)

References 19 publications

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“…231 GnRH can be administered at different pulse frequencies across the cycle, mimicking physiological ovarian stimulation. 232 Alternatively, pulsatile GnRH at a constant frequency also induces maturation of ovarian follicles and triggers an LH peak. The usual doses comprise 3-10 μg per pulse, injected subcutaneously every 90 min.…”

Section: Induction Of Female Sexual Characteristicsmentioning

confidence: 99%

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

et al. 2015

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| Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ~50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRHsynthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ~10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.

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Section: Induction Of Female Sexual Characteristicsmentioning

confidence: 99%

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

et al. 2015

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“…Pulsatile gonadotropin releasing hormone (GnRH) treatment is an appropriate and effective way to establish normal ovarian function [Crowley and McArthur 1980]. But many patients display psychological problems and are agitated by having to carry an electronic pump on their body for a long time.…”

Section: Introductionmentioning

confidence: 99%

The reproductive outcome of women with hypogonadotropic hypogonadism undergoingin vitrofertilization

Yılmaz

Özgü-Erdinç

Yumusak

et al. 2015

Systems Biology in Reproductive Medicine

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The aim of this study was to evaluate the reproductive outcome and assisted reproductive technology (ART) outcomes of patients with hypogonadotropic hypogonadism (HH) and to compare the results with male factor (MF) infertility patients. The reproductive outcome of 33 HH patients was evaluated retrospectively and compared with results of 47 patients with mild male factor infertility. For ovulation induction, human menopausal gonadotropin (hMG) was used in HH patients and recFSH was used in MF infertility patients. HH patients were divided into subgroups according to retrieved oocyte numbers and the groups were compared with each other. The main outcome measures were total gonadotropin dose used, duration of stimulation, human chorionic gonadotropin (hCG) day estradiol level and endometrial thickness, oocyte number retrieved, and rate of clinical pregnancy. ART outcomes and cycle characteristics of 33 HH patients were compared with 47 MF infertility patients. There was no difference in age and body mass index (BMI) between the groups, but mean follicle stimulating hormone FSH and luteinizing hormone LH levels were significantly lower in the HH group (p50.001). Duration of stimulation was 12.5 ± 2.06 days in the HH patients and 10.08 ± 1.62 days in the MF infertility patients and the difference was significant (p50.001). Total gonadotropin dose used was higher in the HH group than the MF infertility group (p 5 0.001). However, there were no differences in hCG day estradiol levels, endometrial thickness on hCG day, total oocyte number retrieved, MII oocyte number, and pregnancy rate. In the HH subgroups, patient ages were significantly lower in the 415 oocyte retrieved group. Although patients with HH have a long-term estrogen deficiency, their response to controlled ovarian hyperstimulation treatment is similar to normal women. However, the HH group is heterogeneous and estimating the ovarian reserve before treatment is not always possible in this group.

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“…Finally, recent studies have demonstrated that the frequency of GnRH stimulation may itself be a critical determinant of the pituitary response to GnRH. Whereas physiological frequencies of GnRH stimulation maintain normal gonadotropin secretion in GnRH-deficient animals (1, 10, 11) and humans (12)(13)(14)(15), supraphysiological frequencies of GnRH administration produce pituitary desensitization (1,10,(16)(17)(18). In contrast, slow frequencies of GnRH stimulation increase the amplitude ofthe LH pulse in GnRH-deficient animals (10,11,19).…”

Section: Introductionmentioning

confidence: 99%

Effects of decreasing the frequency of gonadotropin-releasing hormone stimulation on gonadotropin secretion in gonadotropin-releasing hormone-deficient men and perifused rat pituitary cells.

Finkelstein¹,

Badger²,

O’Dea³

et al. 1988

J. Clin. Invest.

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The effects of decreasing the frequency of pulsatile gonadotropin-releasing hormone (GnRH) stimulation on pituitary responsiveness were studied in (a) men with isolated GnRH deficiency who had achieved normal sex steroid levels during prior long-term pulsatile GnRH replacement and (b) perifused dispersed pituitary cells from male rats in the absence of sex steroids. In three groups of four GnRH-deficient men, the frequency of GnRH stimulation was decreased at weekly intervals from (a) every 2-34 h (group I), (b) every 2-8 h without testosterone replacement (group II), or (c) every 2-8 h with testosterone replacement (group III). In three groups of three columns of perifused dispersed pituitary cells, pulses of GnRH were administered every 2, 4, or 8 h.In groups I and II, mean area under the luteinizing hormone (LH) curve increased (P < 0.025) and serum testosterone levels fell (P < 0.035) as the frequency of GnRH stimulation was decreased. In group III, the area under the LH curve also increased (P < 0.01) although serum testosterone levels were constant, thereby demonstrating that the increase in pituitary responsiveness to slow frequencies of GnRH stimulation occurs independently of changes in the sex steroid hormonal milieu. The area under the LH curve also increased in the perifused dispersed rat pituitary cells when the frequency of GnRH administration was decreased to every 8 h (P < 0.05), thus demonstrating that the enhanced pituitary responsiveness to slow frequencies of GnRH stimulation is maintained even in the complete absence of gonadal steroids.Nadir LH levels fell in all three groups (P < 0.01) as the frequency of GnRH stimulation was decreased. In contrast, mean peak LH levels, the rate of LH rise, and the rate of endogenous LH decay were constant as the frequency ofGnRH stimulation was decreased. Finally, as the GnRH interpulse interval increased, mean LH levels fell, and mean follicle-stimulating hormone levels were stable or fell.

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Simulation of the Normal Menstrual Cycle in Kallman's Syndrome by Pulsatile Administration of Luteinizing Hormone-Releasing Hormone (Lhrh)

Cited by 293 publications

References 19 publications

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

The reproductive outcome of women with hypogonadotropic hypogonadism undergoingin vitrofertilization

Effects of decreasing the frequency of gonadotropin-releasing hormone stimulation on gonadotropin secretion in gonadotropin-releasing hormone-deficient men and perifused rat pituitary cells.

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