Trial Outcomes & Findings for Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone (NCT NCT01427595)

Last Updated: 2021-01-08

Results Overview

The progesterone (P4) sensitivity index is defined as the percent change in 11-hour LH pulse frequency before and after P4 and estradiol administration for 7 days, divided by the day 7 mean serum P4 concentration. We compared the P4 sensitivity index after metformin administration to the baseline P4 sensitivity index, using Wilcoxon signed-rank test.

Recruitment status

COMPLETED

Study phase

Target enrollment

25 participants

Primary outcome timeframe

12 weeks following start of metformin treatment

Results posted on

2021-01-08

Participant Flow

25 subjects enrolled in this study. 7 subjects completed screening procedures only (these 7 subjects were withdrawn from study prior to being assigned to an arm of intervention).

Participant milestones

Participant milestones
Measure	Metformin, Progesterone , Estrace 12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X) Metformin: 500-2000 mg PO BID (X12 weeks) Progesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2) estrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2
Overall Study STARTED	25
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin, Progesterone , Estrace n=10 Participants 12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X) Metformin: 500-2000 mg PO BID (X12 weeks) Progesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2) estrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2
Age, Categorical <=18 years	10 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	15.3 years STANDARD_DEVIATION 1.2 • n=93 Participants
Sex: Female, Male Female	10 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	8 Participants n=93 Participants
Race (NIH/OMB) More than one race	2 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	10 participants n=93 Participants

PRIMARY outcome

Timeframe: 12 weeks following start of metformin treatment

Population: 12 subjects completed study but 2 subjects were excluded from analysis due to incomplete adherence to metformin, missing \> 10% of doses.

Outcome measures

Outcome measures
Measure	Metformin, Progesterone , Estrace n=10 Participants 12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X) Metformin: 500-2000 mg PO BID (X12 weeks) Progesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2) estrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2
Change in Progesterone Sensitivity Index Before and After Metformin Treatment. Before Metformin	-4.12 % change in LH pulses/day 7 P4 level Standard Deviation 2.39
Change in Progesterone Sensitivity Index Before and After Metformin Treatment. After Metformin	-4.29 % change in LH pulses/day 7 P4 level Standard Deviation 7.66

Adverse Events

Metformin, Progesterone , Estrace

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Metformin, Progesterone , Estrace n=25 participants at risk 12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X) Metformin: 500-2000 mg PO BID (X12 weeks) Progesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2) estrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2
Eye disorders Vision switched from near to farsighted	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
Cardiac disorders SVT	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
Infections and infestations Infection	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
General disorders headache	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
General disorders nausea	8.0% 2/25 • Number of events 2 • From start of study procedures until 30 days post study drug.
Infections and infestations UTI	12.0% 3/25 • Number of events 3 • From start of study procedures until 30 days post study drug.
General disorders fainting	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
Gastrointestinal disorders diarrhea	8.0% 2/25 • Number of events 2 • From start of study procedures until 30 days post study drug.
Gastrointestinal disorders Acute Gastroenteritis	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
General disorders heartburn	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
Gastrointestinal disorders vomitting	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.
Skin and subcutaneous tissue disorders rash	4.0% 1/25 • Number of events 1 • From start of study procedures until 30 days post study drug.

Additional Information

Dr. Christine Burt Solorzano

University of Virginia Center for Research in Reproduction

Phone: 4342436911

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place