Trial Outcomes & Findings for T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin (NCT NCT01686828)

Last Updated: 2018-05-08

Results Overview

Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG\*FI)\*(FPG+PG30\*2+PG60\*2+PG90\*2+PG120)/8\*(FPI+PI30\*2+PI60\*2+PI90\*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

53 participants

Primary outcome timeframe

4 weeks

Results posted on

2018-05-08

Participant Flow

Recruitment period: 06/01/13-11/30/2014 Location: University/Medical Center Flyers, newspaper ads, online postings

116 subjects were screened, 63 subjects didn't meet study inclusion/exclusion criteria or they withdrew consent prior to group assignment, and 3 subjects withdrew prior to the baseline visit.

Participant milestones

Participant milestones
Measure	Acyline & Placebo Gel & Placebo Pill Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Overall Study STARTED	13	14	13	13
Overall Study COMPLETED	12	13	12	13
Overall Study NOT COMPLETED	1	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Acyline & Placebo Gel & Placebo Pill Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
Overall Study Physician Decision	1	0	0
Overall Study New Job	0	1	0
Overall Study Weight Loss	0	0	1

Baseline Characteristics

T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acyline & Placebo Gel & Placebo Pill n=13 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill n=14 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill n=13 Participants Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole n=13 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks	Total n=53 Participants Total of all reporting groups
Age, Continuous	37 years n=5 Participants	35 years n=7 Participants	42 years n=5 Participants	34 years n=4 Participants	36 years n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	13 Participants n=4 Participants	53 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	13 Participants n=4 Participants	44 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	37 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	9 Participants n=21 Participants
Region of Enrollment United States	13 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	13 participants n=4 Participants	53 participants n=21 Participants
Body Mass Index (BMI)	26 kg/m2 STANDARD_DEVIATION 4 • n=5 Participants	26 kg/m2 STANDARD_DEVIATION 4 • n=7 Participants	25 kg/m2 STANDARD_DEVIATION 2 • n=5 Participants	25 kg/m2 STANDARD_DEVIATION 4 • n=4 Participants	25 kg/m2 STANDARD_DEVIATION 3 • n=21 Participants
Weight	82 kg STANDARD_DEVIATION 14 • n=5 Participants	81 kg STANDARD_DEVIATION 15 • n=7 Participants	78 kg STANDARD_DEVIATION 8 • n=5 Participants	82 kg STANDARD_DEVIATION 11 • n=4 Participants	81 kg STANDARD_DEVIATION 12 • n=21 Participants
Fasting Glucose	97 mg/dL STANDARD_DEVIATION 6 • n=5 Participants	97 mg/dL STANDARD_DEVIATION 13 • n=7 Participants	101 mg/dL STANDARD_DEVIATION 7 • n=5 Participants	98 mg/dL STANDARD_DEVIATION 9 • n=4 Participants	98 mg/dL STANDARD_DEVIATION 9 • n=21 Participants
Percentage Body Fat	28 %total body mass STANDARD_DEVIATION 7 • n=5 Participants	23 %total body mass STANDARD_DEVIATION 6 • n=7 Participants	24 %total body mass STANDARD_DEVIATION 4 • n=5 Participants	23 %total body mass STANDARD_DEVIATION 7 • n=4 Participants	24 %total body mass STANDARD_DEVIATION 6 • n=21 Participants
Percentage Lean Mass	68 %total body mass STANDARD_DEVIATION 7 • n=5 Participants	73 %total body mass STANDARD_DEVIATION 5 • n=7 Participants	72 %total body mass STANDARD_DEVIATION 4 • n=5 Participants	73 %total body mass STANDARD_DEVIATION 7 • n=4 Participants	72 %total body mass STANDARD_DEVIATION 6 • n=21 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Of the 53 subjects who attended the baseline study visit, 2 withdrew from the study and 1 was discontinued due to a protocol violation. 50 subjects completed the week 10 study visit. Of these, 5 subjects were excluded from the final analyses; 1 was found to have undiagnosed diabetes, and 4 subjects were excluded due to study drug non-adherence.

Outcome measures

Outcome measures
Measure	Acyline & Placebo Gel & Placebo Pill n=10 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill n=11 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill n=11 Participants Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole n=13 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Insulin Sensitivity Quantified by Matsuda Index	5.0 units on a scale Interval 3.9 to 6.3	9.4 units on a scale Interval 4.5 to 14.0	7.2 units on a scale Interval 4.6 to 15.0	7.3 units on a scale Interval 5.9 to 10.0

SECONDARY outcome

Timeframe: 4 weeks

Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period

Outcome measures

Outcome measures
Measure	Acyline & Placebo Gel & Placebo Pill n=10 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill n=11 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill n=11 Participants Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole n=13 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Changes in Body Composition Change in fat mass	1.1 kg Standard Deviation 0.8	0.7 kg Standard Deviation 0.5	-0.4 kg Standard Deviation 1.0	0.5 kg Standard Deviation 0.8
Changes in Body Composition Change in lean mass	-1.2 kg Standard Deviation 1.0	-1.4 kg Standard Deviation 1.5	0.0 kg Standard Deviation 1.0	-0.3 kg Standard Deviation 1.3

SECONDARY outcome

Timeframe: 4 weeks

Population: Subjects were included who had adipose tissue samples available from both baseline and week 4 (end-of-treatment) visits.

We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s.

Outcome measures

Outcome measures
Measure	Acyline & Placebo Gel & Placebo Pill n=10 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill n=11 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill n=11 Participants Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole n=13 Participants Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Changes in Adipose Tissue Gene Expression	7493 gene copy number per ng RNA Standard Deviation 1293	8224 gene copy number per ng RNA Standard Deviation 3485	7885 gene copy number per ng RNA Standard Deviation 2736	8320 gene copy number per ng RNA Standard Deviation 3133

Adverse Events

Acyline & Placebo Gel & Placebo Pill

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Acyline & Testosterone Gel 1.25g/d & Placebo Pill

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Acyline & Testosterone Gel 5g/d & Placebo Pill

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Acyline & Testosterone Gel & Letrozole

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Acyline & Placebo Gel & Placebo Pill n=13 participants at risk Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill n=14 participants at risk Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill n=13 participants at risk Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole n=13 participants at risk Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Cardiac disorders Cardiac Arrthymia	7.7% 1/13 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/14 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
Hepatobiliary disorders Abnormal Liver enzyme (AST & ALT) levels	7.7% 1/13 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/14 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
Endocrine disorders Elevated PSA level	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	7.1% 1/14 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.

Other adverse events

Other adverse events
Measure	Acyline & Placebo Gel & Placebo Pill n=13 participants at risk Acyline (300mcg/kg at Day 0 \& week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 1.25g/d & Placebo Pill n=14 participants at risk Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel 5g/d & Placebo Pill n=13 participants at risk Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d	Acyline & Testosterone Gel & Letrozole n=13 participants at risk Acyline (300mcg/kg at Day 0 \& week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Endocrine disorders Hot Flashes	23.1% 3/13 • Number of events 3 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	7.1% 1/14 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	7.7% 1/13 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
Endocrine disorders Low libido	30.8% 4/13 • Number of events 4 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	28.6% 4/14 • Number of events 4 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	38.5% 5/13 • Number of events 5 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
Nervous system disorders Erectile Dysfunction	15.4% 2/13 • Number of events 2 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/14 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	15.4% 2/13 • Number of events 2 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
General disorders Low Energy	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	21.4% 3/14 • Number of events 3 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	7.7% 1/13 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	7.7% 1/13 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
General disorders Irritability	15.4% 2/13 • Number of events 2 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/14 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	7.7% 1/13 • Number of events 1 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
Endocrine disorders Decreased testes size	30.8% 4/13 • Number of events 4 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	14.3% 2/14 • Number of events 2 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	15.4% 2/13 • Number of events 2 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.
General disorders Fatigue	0.00% 0/13 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	0.00% 0/14 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	23.1% 3/13 • Number of events 3 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.	15.4% 2/13 • Number of events 2 • Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended. There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of \>15% was used for reported events.

Additional Information

Dr. Katya Rubinow

University of Washington

Phone: 206-7543-3470

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place