Trial Outcomes & Findings for Pre-Exposure Prophylaxis (PrEP)- Gender Affirming Hormone Therapy (GAHT) Interactions in TGW (NCT NCT04760691)

Last Updated: 2026-04-06

Results Overview

Plasma TFV Cmax was defined as the highest observed concentration during the 24 hour (h) dosing interval and determined via non-compartmental analyses. Median maximum concentrations with interquartile ranges (IQR) were determined. Differences in TFV Cmax concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in TFV Cmax, with IQRs, was calculated.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.

Results posted on

2026-04-06

Participant Flow

Each participant who enrolled completed all 5 phases(arms) of the study. Therefore, each participant results is included in each arm of the study.

Participant milestones

Participant milestones
Measure	Pre-Exposure Prophylaxis (PrEP) Only Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg intramuscular injection once	PrEP Plus Low Dose Estrogen Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	PrEP Plus High Dose Estrogen Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily	High Dose Estrogen Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily
Pre-exposure Prophylaxis Only (1 Week) STARTED	13	0	0	0	0
Pre-exposure Prophylaxis Only (1 Week) COMPLETED	13	0	0	0	0
Pre-exposure Prophylaxis Only (1 Week) NOT COMPLETED	0	0	0	0	0
PrEP Plus GRH (1 Week) STARTED	0	13	0	0	0
PrEP Plus GRH (1 Week) COMPLETED	0	13	0	0	0
PrEP Plus GRH (1 Week) NOT COMPLETED	0	0	0	0	0
PrEP Plus Low Dose Estrogen (1 Week) STARTED	0	0	13	0	0
PrEP Plus Low Dose Estrogen (1 Week) COMPLETED	0	0	13	0	0
PrEP Plus Low Dose Estrogen (1 Week) NOT COMPLETED	0	0	0	0	0
PrEP Plus High Dose Estrogen (1 Week) STARTED	0	0	0	13	0
PrEP Plus High Dose Estrogen (1 Week) COMPLETED	0	0	0	13	0
PrEP Plus High Dose Estrogen (1 Week) NOT COMPLETED	0	0	0	0	0
High Dose Estrogen (1 Week) STARTED	0	0	0	0	13
High Dose Estrogen (1 Week) COMPLETED	0	0	0	0	13
High Dose Estrogen (1 Week) NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pre-Exposure Prophylaxis (PrEP)- Gender Affirming Hormone Therapy (GAHT) Interactions in TGW

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enrolled Participants n=13 Participants Enrolled participants at baseline
Age, Continuous	26 years n=5 Participants
Sex/Gender, Customized Transgender women	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Baseline testosterone	503 ng/dL n=5 Participants
Baseline creatinine	0.90 mg/dL n=5 Participants
Baseline cystatin C	0.83 mg/L n=5 Participants
Baseline mGFR	115 mL/min/1.73 m^2 n=5 Participants

PRIMARY outcome

Timeframe: Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in Maximum Tenofovir Plasma (Cmax) Concentration Median plasma TFV Cmax (ng/mL)	274 ng/mL Interval 231.0 to 331.0	0.165 ng/mL Interval 0.165 to 0.336	286 ng/mL Interval 274.0 to 358.0	276 ng/mL Interval 237.0 to 343.0	277 ng/mL Interval 196.0 to 319.0
Change in Maximum Tenofovir Plasma (Cmax) Concentration Median intra-individual difference TFV Cmax (ng/mL) from PrEP Only Dosing Period	-23 ng/mL Interval -63.0 to 47.0	-285 ng/mL Interval -357.0 to -274.0	NA ng/mL The PrEP only dosing period is the reference measurement for this assessment. Therefore, a change in this measurement cannot be calculated.	-16 ng/mL Interval -32.0 to 57.0	-27 ng/mL Interval -123.0 to 0.2

PRIMARY outcome

The reported AUC is the area under the curve of the concentration-time curve calculated using trapezoidal rule (sum of trapezoids) over a 24h period (AUC0-24h). Median AUCs and IQRs were determined. Changes in AUC0-24h from baseline were based on comparisons between the reported AUC during each dosing period. Differences in the TFV AUC0-24h were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the TFV AUC0-24h, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in Calculated Plasma TFV Area Under the Concentration-Time Curve (AUC0-24h) Median Plasma TFV are under the curve	2726 hr*ng/mL Interval 1860.0 to 2986.0	NA hr*ng/mL AUC was calculated based on trapezoidal rule of TFV concentrations measured over a 24 hour period. There was an insufficient number of events to calculate the TFV AUC at this timepoint.	2640 hr*ng/mL Interval 2578.0 to 3419.0	2504 hr*ng/mL Interval 2150.0 to 3306.0	2464 hr*ng/mL Interval 2077.0 to 2871.0
Change in Calculated Plasma TFV Area Under the Concentration-Time Curve (AUC0-24h) Median intra-individua Difference in TFV area under the curve from PrEP Only Dosing Period	-421 hr*ng/mL Interval -782.0 to -67.0	NA hr*ng/mL AUC was calculated based on trapezoidal rule of TFV concentrations measured over a 24 hour period. There was an insufficient number of events to calculate the TFV AUC at this timepoint.	NA hr*ng/mL The PrEP only dosing period is the reference measurement for this assessment. Therefore, a change in this measurement cannot be calculated.	-31 hr*ng/mL Interval -519.0 to 210.0	-352 hr*ng/mL Interval -902.0 to -67.0

PRIMARY outcome

Timeframe: Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen.

The PBMC TFV-DP (fmol/10\^6 cells) concentration was measured at 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median PBMC TFV-DP concentrations, normalized to millions of cells analyzed, were measured. Differences in the PBMC TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the PBMC TFV-DP Concentrations, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in PBMC TFV-DP C24 Concentration Median intra-individual Difference in PBMC TFV-DP from PrEP Only Dosing Period	34 fmol/10^6 cells Interval 13.0 to 45.0	-51 fmol/10^6 cells Interval -58.0 to -40.0	NA fmol/10^6 cells The PrEP only dosing period is the reference measurement for this assessment. Therefore, a change in this measurement cannot be calculated.	19 fmol/10^6 cells Interval 5.8 to 35.0	41 fmol/10^6 cells Interval 12.0 to 52.0
Change in PBMC TFV-DP C24 Concentration Median PBMC TFV-DP	94 fmol/10^6 cells Interval 76.0 to 113.0	11 fmol/10^6 cells Interval 7.0 to 14.0	59 fmol/10^6 cells Interval 54.0 to 73.0	81 fmol/10^6 cells Interval 66.0 to 100.0	101 fmol/10^6 cells Interval 86.0 to 124.0

PRIMARY outcome

The estimated colon TFV-DP was measured from colon biopsies 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median colon tissue TFV-DP concentrations (with IQRs), normalized to weight of tissue biopsy analyzed, were measured. Differences in the colonic tissue TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the colonic tissue TFV-DP concentrations, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in TFV-DP Colon Tissue Concentration Median Tissue TFV-DP	1374 fmol/mg Interval 748.0 to 4084.0	5.61 fmol/mg Interval 3.14 to 11.5	951 fmol/mg Interval 564.0 to 1272.0	1973 fmol/mg Interval 540.0 to 4952.0	1569 fmol/mg Interval 400.0 to 3985.0
Change in TFV-DP Colon Tissue Concentration Median intra-individual difference in Tissue TFV-DP from PrEP Only Dosing Period	38 fmol/mg Interval -199.0 to 3944.0	-940 fmol/mg Interval -1261.0 to -561.0	NA fmol/mg The PrEP only dosing period is the reference measurement for this assessment. Therefore, a change in this measurement cannot be calculated.	478 fmol/mg Interval -20.0 to 4001.0	570 fmol/mg Interval -13.0 to 2713.0

SECONDARY outcome

Timeframe: Day 7 for Pre-Exposure Prophylaxis (PrEP) Only, Day 21 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 28 for PrEP Plus Lose-Dose Estrogen, Day 35 for PrEP Plus High-Dose Estrogen, and Day 49 for High-Dose Estrogen

The measured serum estradiol concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Differences in the serum estradiol concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum estradiol concentrations, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in Serum Estradiol Concentration Median Estradiol	17 pg/mL Interval 9.0 to 20.0	107 pg/mL Interval 76.0 to 124.0	21 pg/mL Interval 14.0 to 28.0	9 pg/mL Interval 6.0 to 10.0	92 pg/mL Interval 71.0 to 119.0
Change in Serum Estradiol Concentration Median intra-individual Difference from Baseline	-4.6 pg/mL Interval -12.0 to -2.6	77 pg/mL Interval 58.0 to 105.0	-1.6 pg/mL Interval -5.2 to 1.8	-13 pg/mL Interval -18.0 to -7.3	75 pg/mL Interval 57.0 to 89.0

SECONDARY outcome

The measured percent free testosterone at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median percent free testosterone measurements, with interquartile range, were measured. Differences in the percent free testosterone were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in percent free testosterone, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in Serum Free Testosterone Median Free Testosterone	3.51 Percent free testosterone Interval 2.48 to 4.93	3.36 Percent free testosterone Interval 2.49 to 5.18	3.19 Percent free testosterone Interval 2.69 to 3.19	3.22 Percent free testosterone Interval 1.96 to 3.59	3.54 Percent free testosterone Interval 3.08 to 4.63
Change in Serum Free Testosterone Median intra-individual Difference from Baseline	-0.025 Percent free testosterone Interval -1.03 to 0.805	-0.195 Percent free testosterone Interval -0.548 to 0.883	-0.465 Percent free testosterone Interval -0.675 to -0.193	-0.585 Percent free testosterone Interval -1.51 to -0.03	-0.950 Percent free testosterone Interval -1.08 to 1.06

SECONDARY outcome

The measured serum total testosterone concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median serum total testosterone concentrations, with interquartile range, were measured. Differences in serum testosterone concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum testosterone concentrations, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in Serum Total Testosterone Concentration Median Total Testosterone	60.5 ng/dL Interval 41.0 to 72.0	41 ng/dL Interval 25.0 to 103.0	490 ng/dL Interval 396.0 to 554.0	151 ng/dL Interval 121.0 to 274.0	43 ng/dL Interval 27.0 to 56.0
Change in Serum Total Testosterone Concentration Median intra-individual Difference from Baseline	-432 ng/dL Interval -510.0 to -320.0	-445 ng/dL Interval -500.0 to -315.0	-18 ng/dL Interval -81.0 to 41.0	-298 ng/dL Interval -346.0 to -219.0	-448 ng/dL Interval -523.0 to -340.0

SECONDARY outcome

The measured serum LH concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median serum LH concentrations, with interquartile range, were measured. Differences in serum LH concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum LH concentrations, with IQRs, was calculated.

Outcome measures

Outcome measures
Measure	PrEP Plus Low Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks Truvada plus Estradiol 1 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily	High Dose Estrogen n=13 Participants Estradiol 6 mg by mouth daily x 2 weeks Estradiol 6 mg alone: Estradiol 3 mg by mouth twice daily	Pre-Exposure Prophylaxis (PrEP) Only n=13 Participants Truvada one tablet by mouth daily Truvada alone: TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily	PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist n=13 Participants Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once Truvada plus Leuprolide: TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg im injection once	PrEP Plus High Dose Estrogen n=13 Participants Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks Truvada plus Estradiol 6 mg: TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
Change in Serum Luteinizing Hormone (LH) Concentration Median LH	1.23 mIU/mL Interval 1.2 to 1.74	1.66 mIU/mL Interval 0.76 to 2.46	4.19 mIU/mL Interval 3.07 to 4.92	2.73 mIU/mL Interval 2.28 to 3.76	1.60 mIU/mL Interval 1.15 to 3.16
Change in Serum Luteinizing Hormone (LH) Concentration Median intra-individual Difference from Baseline	-2.37 mIU/mL Interval -4.1 to -1.8	-2.13 mIU/mL Interval -3.52 to -0.91	-0.01 mIU/mL Interval -0.45 to 0.69	-1.59 mIU/mL Interval -2.6 to -0.29	-2.05 mIU/mL Interval -3.38 to -1.32

SECONDARY outcome

The measured serum FSH concentration at the beginning of the intensive PK-sampling visit for the preceding evaluated dosing period. Median serum FSH concentrations, with interquartile range, were measured. Differences in serum FSH concentrations were determined for each participant, and each dosing period was compared to baseline visit (no PrEP and no hormone supplementation). The median intra-individual difference in serum FSH concentrations, with IQRs, was calculated.