Dataset Information

Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

ABSTRACT: INTRODUCTION:Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to "castrate" levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ?20 ng/dL levels. METHODS:In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. RESULTS:Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ?20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ?20 ng/dL at 48 weeks. CONCLUSION:Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ?20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

SUBMITTER: Spitz A

PROVIDER: S-EPMC5003568 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

Spitz Aaron A Gittelman Marc M Karsh Lawrence I LI Dragnic Sanja S Soliman Ahmed M AM Lele Aditya A Gruca Damian D Norton Michael M

Research and reports in urology 20160823

<h4>Introduction</h4>Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to "castrate" levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate ( ...[more]

PMID: 27602344

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Project description:Abstract Context Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dL is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study investigating whether baseline T levels also influences body composition and metabolic response to T therapy. Objective To determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with baseline T level of < 264 ng/dL compared to those with levels ≥264ng/dL Methods: Secondary analysis of single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011-2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dL, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of < 264 ng/dL (N=43) and those with ≥264 ng/dL (N=57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, sclerostin), adiponectin, and leptin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD, and body composition by dual-energy x-ray absorptiometry (DXA). Results Men with T < 264 ng/dL showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dL (4.2±4.1 vs 2.7±3.8%; p=0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7±11.5 vs 4.4±4.3%, 7.3±11.6 vs 2.4±6.8%; p=0.033 and p=0.043, respectively). Men with T ≥ 264 ng/dL showed significant decreases in HbA1c at 12 months (-3.1±9.2 vs 3.2±13.9%; p=0.005), fasting glucose at 18 months (-4.2±31.9 vs 13.0±57.3%; p=0.040), LDL at 6 months (-6.4±27.5 vs 12.8±44.1%; p=0.034), leptin at 18 months (-40.2±35.1 vs -27.6±31.0%; p=0.034) compared to those with T < 264 ng/dL. No significant differences in BMD and bone turnover markers were observed. Conclusion T therapy results in improvement in body composition irrespective of baseline T levels but T <264 ng/dL is associated with greater improvement in FFM, whereas T level of ≥264 ng/dL favors improvement in metabolic profile. Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.

Project description:ObjectiveTo examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development.Study designWe assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14?mm, 15-17?mm and?? 18?mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24?h after DMPA administration to examine against ovulatory outcomes.ResultsTwenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14?mm: 0/10 (0%); 15-17?mm: 3/10 (30%); ? 18?mm: 6/6 (100%); p?<?.01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7?IU/L (mean 49.0?IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression.ConclusionDMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge.ImplicationsDMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.

Project description:BackgroundThe vaginal microbiome plays a key role in women's reproductive health. Use of exogenous hormones, such as intramuscular depot medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community.MethodsVaginal swab samples were collected from postpartum Kenyan women initiating DMPA-IM or nonhormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S ribosomal RNA gene polymerase chain reaction with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to 3 months after initiation were estimated using multivariable linear mixed effects regression.ResultsAmong 54 human immunodeficiency virus-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (change, -1.89; 95% confidence interval [CI], -3.53 to -.25; P = .02) while alpha diversity remained stable (0.03; -.24 to .30; P = .83). Conversely, Nugent score remained relatively stable among non-HC users (change, -0.73; 95% CI, -2.18 to .73; P = .33) while alpha diversity decreased (-0.34; -.67 to -.001; P = .05). The total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference, -0.64 log10 gene copies per swab sample; 95% CI, -1.19 to -.08; P = .02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different.ConclusionsPostpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but it decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women.

Dataset Information

Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

Publications

Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

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