Browsing by Subject "Gonadotropin-Releasing Hormone"
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Item Open Access Hormone naïve prostate cancer: predicting and maximizing response intervals.(Asian journal of andrology, 2015-11) Moul, Judd WHormone naïve advanced prostate cancer is subdivided into two disease states: biochemical recurrence and traditional M1 (metastatic) prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy (ADT). In biochemical recurrence/prostate-specific antigen (PSA) recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade (peripheral androgen deprivation) to complete hormonal therapy (combined androgen blockade [CAB]) remains in debate owing to lack of randomized controlled trials (RCT). However, there is good RCT support for use of intermittent hormonal therapy (IHT). There is also limited research on biomarker response (PSA and testosterone decline) to predict prognosis. On the other hand, in the setting of M1 hormone naïve prostate cancer, there are many more RCT's to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone (T) control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M1 patient, maintaining a serum T below 20-30 ng dl-1 prolongs the response to ADT. Novel oral agents (abiraterone and enzalutamide) may soon find use in hormone naïve disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.Item Open Access Pre-IVF treatment with a GnRH antagonist in women with endometriosis (PREGNANT): study protocol for a prospective, double-blind, placebo-controlled trial.(BMJ open, 2022-06) Taylor, Hugh; Li, Howard J; Carson, Sandra; Flores, Valerie; Pal, Lubna; Robbins, Jared; Santoro, Nanette F; Segars, James H; Seifer, David; Huang, Hao; Young, Steven; Zhang, HepingIntroduction
Infertility is a common complication of endometriosis. While in vitro fertilisation-embryo transfer (IVF) successfully treats endometriosis-associated infertility, there is some evidence that pregnancy rates may be diminished in women seeing fertility treatment for endometriosis-associated infertility compared with other etiologies of infertility. The use of gonadotropin releasing hormone (GnRH) agonist prior to IVF has been suggested to improve success, however studies have been small and rarely reported live birth rates. Recent approval of an oral GnRH antagonist for endometriosis provides a novel option for women with endometriosis who are undergoing IVF. There have been no studies on the efficacy of GnRH antagonists for the treatment of endometriosis-related infertility.Methods and analysis
This study is a multicentre, prospective, randomised, double-blind, placebo-controlled trial to study the efficacy of GnRH antagonist pretreatment for women with endometriosis who are undergoing IVF. A total of 814 patients with endometriosis undergoing fertility treatment will be enrolled and randomised 1:1 into two groups: elagolix 200 mg two times per day or placebo for 8 weeks, prior to undergoing IVF. All participants will then undergo IVF treatment per local protocols. The primary outcome is live birth. Secondary outcomes include oocyte number, fertilisation rate, embryo morphology and implantation rates, as well as rates of known endometriosis-related obstetrical outcomes (pregnancy-induced hypertension, antepartum haemorrhage, caesarean delivery and preterm birth).Ethics and dissemination
The PREGnant trial was approved by the Institutional Review Board at Johns Hopkins University. Results will be published in a peer-reviewed journal.Trial registration number
NCT04173169.Item Open Access Rapid behavioral and genomic responses to social opportunity.(PLoS Biol, 2005-11) Burmeister, SS; Jarvis, ED; Fernald, RDFrom primates to bees, social status regulates reproduction. In the cichlid fish Astatotilapia (Haplochromis) burtoni, subordinate males have reduced fertility and must become dominant to reproduce. This increase in sexual capacity is orchestrated by neurons in the preoptic area, which enlarge in response to dominance and increase expression of gonadotropin-releasing hormone 1 (GnRH1), a peptide critical for reproduction. Using a novel behavioral paradigm, we show for the first time that subordinate males can become dominant within minutes of an opportunity to do so, displaying dramatic changes in body coloration and behavior. We also found that social opportunity induced expression of the immediate-early gene egr-1 in the anterior preoptic area, peaking in regions with high densities of GnRH1 neurons, and not in brain regions that express the related peptides GnRH2 and GnRH3. This genomic response did not occur in stable subordinate or stable dominant males even though stable dominants, like ascending males, displayed dominance behaviors. Moreover, egr-1 in the optic tectum and the cerebellum was similarly induced in all experimental groups, showing that egr-1 induction in the anterior preoptic area of ascending males was specific to this brain region. Because egr-1 codes for a transcription factor important in neural plasticity, induction of egr-1 in the anterior preoptic area by social opportunity could be an early trigger in the molecular cascade that culminates in enhanced fertility and other long-term physiological changes associated with dominance.Item Open Access Willingness of Women with Endometriosis Planning to Undergo IVF to Participate in a Randomized Clinical Trial and the Effects of the COVID-19 Pandemic on Potential Participation.(Reproductive sciences (Thousand Oaks, Calif.), 2022-02) Pretzel, Shannon; Kuhn, Katherine; Pal, Lubna; Polotsky, Alex; Taylor, Hugh S; Zhang, Heping; Robins, Jared; Young, Steven L; Santoro, NanetteThe Pre-IVF Treatment with a GnRH Antagonist in Women with Endometriosis (PREGnant) Trial (clinicaltrials.gov no. NCT04173169) was designed to test the hypothesis that 60-day pre-treatment with an oral GnRH antagonist in women with documented endometriosis and planning an IVF cycle will result in a superior live birth rate to placebo. Eight hundred fourteen women are required from 4 national sites. To determine the feasibility of using an electronic medical record (EMR)-based strategy to recruit 204 participants at the Colorado site, we conducted a survey of women within the UCHealth system. Eligible women, identified using relevant ICD-10 codes, were invited to complete a 6-question survey to assess planned utilization of IVF, potential interest in participation, and whether delays in treatment due to COVID-19 would influence their decision to participate. Of 6354 age-eligible women with an endometriosis diagnosis, 421 had a concurrent infertility diagnosis. After eliminating duplicates, 212 were emailed a survey; 76 (36%) responded, 6 of whom reported no endometriosis diagnosis. Of the remaining 70, 29 (41%) were planning fertility treatment; only 19 planned IVF. All 19 expressed interest in participation. COVID-19 delays in treatment were not considered as a factor affecting participation by 8/19; the remaining 11 felt that it would "somewhat" affect their decision. None reported that they would not consider participation because of COVID-19. EMR-based recruitment for an endometriosis clinical trial is feasible although the overall yield of participants is low. Delays in treatment due to COVID-19 did not appear to overly influence potential recruitment.