Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome

Status

Terminated

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04327934

Enrollment

Registered

2020-03-31

Start date

2017-12-01

Completion date

2022-06-30

Last updated

2024-02-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension, Polycystic Ovary Syndrome

Brief summary

Women with androgen excess polycystic ovary syndrome (AE-PCOS) leads to hypertension.

Detailed description

Our scientific premise is that in AE-PCOS women, the androgen-dominant hormonal milieu causes BP increases via sympathetic activation, vasoconstriction and renal sympathetic nervous system activation. Moreover, this androgen-dominant milieu increases BP via activation of the renin-angiotensin system.

Interventions

DRUGGnRH antagonist

GnRH antagonist up to 16 days.

DRUGGnRH antagonist + MethylTESTOSTERone 5 MG

GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 35 Years

Healthy volunteers

Yes

Inclusion criteria

* Clinical Diagnosis of Polycystic Ovary Syndrome * Able to inject study drug * Able to swallow pills Controls: -Diagnosis of Insulin resistance

Exclusion criteria

* Any woman that does not fit the inclusion criteria * Males

Design outcomes

Primary

Measure	Time frame	Description
Sympathetic Baroreflex	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	microneurography, diastolic blood pressure (finipres) This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in muscle sympathetic nerve activity in response to small changes in blood pressure induced by drug perfusion (modified Oxford).
Final Systolic Blood Pressure	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	SBP at the end of lower body negative pressure
Resting Sympathetic Activity	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Total sympathetic nerve activity
Baroreflex Response to LBNP	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	forearm blood flow (ultrasound)/mean arterial pressure as a linear function of lower body negative pressure. This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in vessel diameter in response to blood pooling (induced by lower body negative pressure).
Free Plasma Testosterone Levels	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Concentration of testosterone in blood.
Renal Response to LBNP	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	POST Lower body negative pressure Plasma renin activity
Renal Responses to LBNP	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	PRE lower body negative pressure Plasma renin activity
Resting Systolic Blood Pressure	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Blood pressure prior to lower body negative pressure

Secondary

Measure	Time frame	Description
Renal Responses	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	P\[ACE\], angiotensin-converting enzyme
Aldosterone	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Plasma aldosterone concentration

Countries

United States

Participant flow

Recruitment details

We will recruit subjects using flyers, our clinics, and social media. Dates 12/01/2017 - 04/29/2022; We were not able to reach recruit goals because our laboratory closed during Covid. When we reopened, we lost a one interested subject, and found greater challenges to recruit subjects.

Participants by arm

Arm	Count
Healthy Control Healthy control participants. GnRH antagonist: GnRH antagonist up to 16 days. GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.	7
AE-PCOS Participants with AE-PCOS. GnRH antagonist: GnRH antagonist up to 16 days. GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.	9
Total	16

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Did not qualify	7	4
Overall Study	Physician Decision	0	1

Baseline characteristics

Characteristic	Healthy Control	AE-PCOS	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	7 Participants	9 Participants	16 Participants
Age, Continuous	28 years STANDARD_DEVIATION 6	24 years STANDARD_DEVIATION 5	26 years STANDARD_DEVIATION 6
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	2 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	7 Participants	13 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) Black or African American	2 Participants	2 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	5 Participants	9 Participants
Region of Enrollment United States	7 participants	9 participants	16 participants
Sex: Female, Male Female	7 Participants	9 Participants	16 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 14	0 / 14
other Total, other adverse events	1 / 14	1 / 14
serious Total, serious adverse events	0 / 14	0 / 14

Outcome results

Primary

Baroreflex Response to LBNP

forearm blood flow (ultrasound)/mean arterial pressure as a linear function of lower body negative pressure. This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in vessel diameter in response to blood pooling (induced by lower body negative pressure).

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Baroreflex Response to LBNP	Baseline	0.98 Arbitrary Units/Beat/mmHg	Standard Deviation 1.35
Healthy Control	Baroreflex Response to LBNP	GnRH antagonist	1.9 Arbitrary Units/Beat/mmHg	Standard Deviation 3
Healthy Control	Baroreflex Response to LBNP	GnRH antagonist with GnRH + Testosterone	0.68 Arbitrary Units/Beat/mmHg	Standard Deviation 0.65
AE-PCOS	Baroreflex Response to LBNP	Baseline	1.36 Arbitrary Units/Beat/mmHg	Standard Deviation 0.96
AE-PCOS	Baroreflex Response to LBNP	GnRH antagonist	4.28 Arbitrary Units/Beat/mmHg	Standard Deviation 6.51
AE-PCOS	Baroreflex Response to LBNP	GnRH antagonist with GnRH + Testosterone	1.46 Arbitrary Units/Beat/mmHg	Standard Deviation 0.76

p-value: 0.018ANOVA

Primary

Final Systolic Blood Pressure

SBP at the end of lower body negative pressure

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Final Systolic Blood Pressure	Baseline	105 mm Hg	Standard Deviation 21
Healthy Control	Final Systolic Blood Pressure	GnRH	109 mm Hg	Standard Deviation 16
Healthy Control	Final Systolic Blood Pressure	GnRH + Testosterone	117 mm Hg	Standard Deviation 16
AE-PCOS	Final Systolic Blood Pressure	GnRH	113 mm Hg	Standard Deviation 12
AE-PCOS	Final Systolic Blood Pressure	Baseline	99 mm Hg	Standard Deviation 23
AE-PCOS	Final Systolic Blood Pressure	GnRH + Testosterone	121 mm Hg	Standard Deviation 10

Primary

Free Plasma Testosterone Levels

Concentration of testosterone in blood.

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Free Plasma Testosterone Levels	Baseline	0.76 mg/dL	Standard Deviation 0.57
Healthy Control	Free Plasma Testosterone Levels	GnRH	0.67 mg/dL	Standard Deviation 0.39
Healthy Control	Free Plasma Testosterone Levels	GnRH + Testosterone	1.34 mg/dL	Standard Deviation 0.23
AE-PCOS	Free Plasma Testosterone Levels	Baseline	2.72 mg/dL	Standard Deviation 1.13
AE-PCOS	Free Plasma Testosterone Levels	GnRH	1.06 mg/dL	Standard Deviation 0.31
AE-PCOS	Free Plasma Testosterone Levels	GnRH + Testosterone	2.19 mg/dL	Standard Deviation 0.19

p-value: <0.016ANOVA

p-value: 0.08ANOVA

Primary

Renal Responses to LBNP

PRE lower body negative pressure Plasma renin activity

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Renal Responses to LBNP	Baseline	0.53 ng/mL ANG/hour	Standard Deviation 0.48
Healthy Control	Renal Responses to LBNP	GnRH	0.42 ng/mL ANG/hour	Standard Deviation 0.21
Healthy Control	Renal Responses to LBNP	GnRH + Testosterone	0.63 ng/mL ANG/hour	Standard Deviation 0.43
AE-PCOS	Renal Responses to LBNP	Baseline	0.85 ng/mL ANG/hour	Standard Deviation 0.97
AE-PCOS	Renal Responses to LBNP	GnRH	0.79 ng/mL ANG/hour	Standard Deviation 1.24
AE-PCOS	Renal Responses to LBNP	GnRH + Testosterone	0.76 ng/mL ANG/hour	Standard Deviation 0.75

Primary

Renal Response to LBNP

POST Lower body negative pressure Plasma renin activity

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Renal Response to LBNP	Baseline	1.05 ng/mL ANG/hour	Standard Deviation 0.82
Healthy Control	Renal Response to LBNP	GnRH	0.54 ng/mL ANG/hour	Standard Deviation 0.33
Healthy Control	Renal Response to LBNP	GnRH+Testosterone	0.83 ng/mL ANG/hour	Standard Deviation 0.71
AE-PCOS	Renal Response to LBNP	GnRH	1.14 ng/mL ANG/hour	Standard Deviation 1.31
AE-PCOS	Renal Response to LBNP	Baseline	1.10 ng/mL ANG/hour	Standard Deviation 0.46
AE-PCOS	Renal Response to LBNP	GnRH+Testosterone	1.36 ng/mL ANG/hour	Standard Deviation 1.51

Primary

Resting Sympathetic Activity

Total sympathetic nerve activity

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Resting Sympathetic Activity	Baseline	14.4 burst/100 heart beats	Standard Deviation 4.4
Healthy Control	Resting Sympathetic Activity	GnRH	7.9 burst/100 heart beats	Standard Deviation 0.8
Healthy Control	Resting Sympathetic Activity	GnRH + Testosterone	13.4 burst/100 heart beats	Standard Deviation 3.6
AE-PCOS	Resting Sympathetic Activity	Baseline	10.3 burst/100 heart beats	Standard Deviation 2
AE-PCOS	Resting Sympathetic Activity	GnRH	6.9 burst/100 heart beats	Standard Deviation 1.5
AE-PCOS	Resting Sympathetic Activity	GnRH + Testosterone	14.5 burst/100 heart beats	Standard Deviation 5

p-value: 0.023t-test, 2 sided

p-value: <0.04ANOVA

Primary

Resting Systolic Blood Pressure

Blood pressure prior to lower body negative pressure

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Population: Systolic Blood Pressure

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Resting Systolic Blood Pressure	Baseline	128 mm Hg	Standard Deviation 15
Healthy Control	Resting Systolic Blood Pressure	GnRH	131 mm Hg	Standard Deviation 10
Healthy Control	Resting Systolic Blood Pressure	GnRH +Testosterone	130 mm Hg	Standard Deviation 12
AE-PCOS	Resting Systolic Blood Pressure	Baseline	123 mm Hg	Standard Deviation 13
AE-PCOS	Resting Systolic Blood Pressure	GnRH	124 mm Hg	Standard Deviation 16
AE-PCOS	Resting Systolic Blood Pressure	GnRH +Testosterone	121 mm Hg	Standard Deviation 16

p-value: 0.05Friedman's test

Primary

Sympathetic Baroreflex

microneurography, diastolic blood pressure (finipres) This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in muscle sympathetic nerve activity in response to small changes in blood pressure induced by drug perfusion (modified Oxford).

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Sympathetic Baroreflex	Baseline	-0.479 Gain (bursts/100 heart beats/ mm Hg)	Standard Deviation 0.085
Healthy Control	Sympathetic Baroreflex	GnRH	-0.468 Gain (bursts/100 heart beats/ mm Hg)	Standard Deviation 0.101
Healthy Control	Sympathetic Baroreflex	GnRH+Testosterone	-0.445 Gain (bursts/100 heart beats/ mm Hg)	Standard Deviation 0.087
AE-PCOS	Sympathetic Baroreflex	GnRH+Testosterone	-0.487 Gain (bursts/100 heart beats/ mm Hg)	Standard Deviation 0.124
AE-PCOS	Sympathetic Baroreflex	Baseline	-0.496 Gain (bursts/100 heart beats/ mm Hg)	Standard Deviation 0.142
AE-PCOS	Sympathetic Baroreflex	GnRH	-0.640 Gain (bursts/100 heart beats/ mm Hg)	Standard Deviation 0.171

p-value: 0.0023ANOVA

Secondary

Aldosterone

Plasma aldosterone concentration

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Aldosterone	Baseline	75.7 pg/mL	Standard Deviation 41.4
Healthy Control	Aldosterone	GnRH	44.0 pg/mL	Standard Deviation 37
Healthy Control	Aldosterone	GnRH+testosterone	46.1 pg/mL	Standard Deviation 28.6
AE-PCOS	Aldosterone	Baseline	136.5 pg/mL	Standard Deviation 60.1
AE-PCOS	Aldosterone	GnRH	127.8 pg/mL	Standard Deviation 70.5
AE-PCOS	Aldosterone	GnRH+testosterone	98.7 pg/mL	Standard Deviation 46.6

p-value: <0.04ANOVA

Secondary

Renal Responses

P\[ACE\], angiotensin-converting enzyme

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Control	Renal Responses	Baseline	38.2 µg/L	Standard Deviation 14.7
Healthy Control	Renal Responses	GnRH	43.4 µg/L	Standard Deviation 27.3
Healthy Control	Renal Responses	GnRH + Testosterone	40.6 µg/L	Standard Deviation 14.1
AE-PCOS	Renal Responses	Baseline	101.9 µg/L	Standard Deviation 93.4
AE-PCOS	Renal Responses	GnRH	77.7 µg/L	Standard Deviation 76.5
AE-PCOS	Renal Responses	GnRH + Testosterone	44.2 µg/L	Standard Deviation 43.2

p-value: <0.04ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Baroreflex Response to LBNP

Final Systolic Blood Pressure

Free Plasma Testosterone Levels

Renal Responses to LBNP

Renal Response to LBNP

Resting Sympathetic Activity

Resting Systolic Blood Pressure

Sympathetic Baroreflex

Aldosterone

Renal Responses