Sexual Absorption of Vaginal Progesterone

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01959464
• Collaborator: Carolinas Medical Center (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if sexual intercourse lowers serum progesterone in women using vaginal progesterone gel (Crinone®), and increases serum progesterone in their male sexual partners. We hypothesize, based on previous estrogen studies done by our group, that intercourse will interfere with absorption of vaginal progesterone.

Condition or Disease	Intervention/Treatment	Phase
Infertility; Pregnancy	Drug: Crinone vaginal progesterone gel; Drug: Placebo vaginal gel	Phase 4

Detailed Description

The effects of intercourse on the absorption of vaginal progesterone for the female user and her sexual partner have not been studied. However, a previous study performed by our group found that intercourse lowered the absorption of vaginal estrogen cream in women, and men absorbed a small but statistically significant amount of estradiol during intercourse. Vaginal progesterone gel may be used by women for several clinical indications, and if intercourse alters the absorption and distribution of vaginal progesterone, clinical outcomes may be compromised. If intercourse lowers absorption, the efficacy of the treatment could be reduced. If intercourse enhances absorption, side effects may be increased. Also, if the male sexual partner absorbs vaginal progesterone, undesirable side effects may occur.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Initial assignment randomized, then crossed over to the other treatmentInitial assignment randomized, then crossed over to the other treatment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Diagnostic
• Official Title: Sexual Absorption of Vaginal Progesterone
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crinone vaginal progesterone gel Crinone is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system containing a water swellable but insoluble polymer, polycarbophil. Crinone 8% is formulated to provide a long-acting vaginal retention, and is prescribed daily. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg of progesterone. The reported time to maximum progesterone concentration is 6.8 +/- 3.3 hours with use of a single dose of Crinone 8%. Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream.	Drug: Crinone vaginal progesterone gel; Crinone vaginal progesterone gel is inserted in the female vaginal using the pre-filled applicator.
Placebo Comparator: Placebo vaginal gel The couple will be given a prefilled applicator containing either Crinone gel (progesterone) or placebo vaginal gel, data collection sheets and laboratory requisitions. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream.	Drug: Placebo vaginal gel; Placebo vaginal gel is inserted in the female vagina using the pre-filled applicator.

Outcome Measures

Primary Outcome Measures

1. Female Change in Progesterone [3 weeks]

   The primary outcome variables will be: the change in serum progesterone levels increase after coitus in the female partner using vaginal progesterone gel compared to placebo

Secondary Outcome Measures

1. Male Change in Progesterone [3 weeks]

   The secondary outcome variable will be the change in serum progesterone levels after coitus in the male partner comparing vaginal progesterone gel and placebo.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Sexually active 18-40 year old heterosexual couple

• Subject willing to take Mircette birth control pills for at least one cycle (one pack)

• Willing to have intercourse at the defined times (at least weekly within a 3 week interval, and draw blood within 10 hours of intercourse)

• IRB signed informed consent

Exclusion Criteria:

• Undiagnosed vaginal bleeding

• Contraindication to oral contraceptives

• Liver dysfunction or disease

• Known sensitivity to Crinone

• Known or suspected malignancy of the breast or genital organs

• History of or active thrombophlebitis or thromboembolic disorders

• Use of condoms during intercourse

• Male erectile or ejaculatory dysfunction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Carolinas Medical Center	Charlotte	North Carolina	United States	28204

Sponsors and Collaborators

• Wake Forest University Health Sciences
• Carolinas Medical Center

Investigators

• Principal Investigator: Bradley S Hurst, MD, Carolinas Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cooper AJ, Sandhu S, Losztyn S, Cernovsky Z. A double-blind placebo controlled trial of medroxyprogesterone acetate and cyproterone acetate with seven pedophiles. Can J Psychiatry. 1992 Dec;37(10):687-93.
• Cooper AJ. Progestogens in the treatment of male sex offenders: a review. Can J Psychiatry. 1986 Feb;31(1):73-9.
• Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;(3):CD004830. Review. Update in: Cochrane Database Syst Rev. 2008;(3):CD004830.
• De Ziegler D, Bulletti C, De Monstier B, Jääskeläinen AS. The first uterine pass effect. Ann N Y Acad Sci. 1997 Sep 26;828:291-9. Review.
• Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9.
• Hurst BS, Jones AI, Elliot M, Marshburn PB, Matthews ML. Absorption of vaginal estrogen cream during sexual intercourse: a prospective, randomized, controlled trial. J Reprod Med. 2008 Jan;53(1):29-32.
• Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994 Sep;62(3):485-90.
• Money J. Treatment guidelines: antiandrogen and counseling of paraphilic sex offenders. J Sex Marital Ther. 1987 Fall;13(3):219-23.
• Polyzos NP, Messini CI, Papanikolaou EG, Mauri D, Tzioras S, Badawy A, Messinis IE. Vaginal progesterone gel for luteal phase support in IVF/ICSI cycles: a meta-analysis. Fertil Steril. 2010 Nov;94(6):2083-7. doi: 10.1016/j.fertnstert.2009.12.058. Epub 2010 Feb 19.
• Practice Committee of the American Society for Reproductive Medicine. Progesterone supplementation during the luteal phase and in early pregnancy in the treatment of infertility: an educational bulletin. Fertil Steril. 2008 Apr;89(4):789-92. doi: 10.1016/j.fertnstert.2008.02.012.
• Practice Committee of the American Society for Reproductive Medicine. The clinical relevance of luteal phase deficiency: a committee opinion. Fertil Steril. 2012 Nov;98(5):1112-7. doi: 10.1016/j.fertnstert.2012.06.050. Epub 2012 Jul 20.
• Watson Pharmaceuticals, Inc. Prescribing Information for Crinone. Available at: http://www.crinoneusa.com/professionals/Prescribing_Information.pdf. Retrieved April 22, 2011.
• Yanushpolsky E, Hurwitz S, Greenberg L, Racowsky C, Hornstein M. Crinone vaginal gel is equally effective and better tolerated than intramuscular progesterone for luteal phase support in in vitro fertilization-embryo transfer cycles: a prospective randomized study. Fertil Steril. 2010 Dec;94(7):2596-9. doi: 10.1016/j.fertnstert.2010.02.033. Epub 2010 Mar 27.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01959464
• Other Study ID Numbers: SAVP2013
• First Posted: Oct 10, 2013
• Last Update Posted: Apr 22, 2022
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Wake Forest University Health Sciences: Assisted reproductive technology; Infertility; Progesterone; Vaginal gel; Luteal-phase support
• Additional relevant MeSH terms: Infertility; Progesterone

Study Results

Participant Flow

Pre-assignment Detail	Women were enrolled into the study to receive the intervention; male partners also had blood samples taken

Arm/Group Title	Placebo Vaginal Gel Then Crinone	Crinone Vaginal Progesterone Gel Then Placebo
Arm/Group Description	The couple will be given a prefilled applicator containing placebo vaginal gel, data collection sheets and laboratory requisitions. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Then they will be crossed over to Crinone vaginal gel.	Crinone is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system containing a water swellable but insoluble polymer, polycarbophil. Crinone 8% is formulated to provide a long-acting vaginal retention, and is prescribed daily. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg of progesterone. The reported time to maximum progesterone concentration is 6.8 +/- 3.3 hours with use of a single dose of Crinone 8%. Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes. On the evening of day 3, the female will insert the applicator into the vagina, administer the Crinone gel, and have intercourse within 1 hour of insertion of the cream. Then subject will cross over to placebo
Period Title: Overall Study
STARTED	10	10
COMPLETED	9	10
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Crinone Vaginal Progesterone Gel Then Placebo	Placebo Vaginal Gel Then Crinone	Total
Arm/Group Description	Crinone is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system containing a water swellable but insoluble polymer, polycarbophil. Crinone 8% is formulated to provide a long-acting vaginal retention, and is prescribed daily. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg of progesterone. The reported time to maximum progesterone concentration is 6.8 +/- 3.3 hours with use of a single dose of Crinone 8%. Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes. On the evening of day 3, the female will insert the applicator into the vagina, administer the Crinone gel, and have intercourse within 1 hour of insertion of the cream. Then she will cross over to placebo.	The couple will be given a prefilled applicator containing placebo vaginal gel, data collection sheets and laboratory requisitions. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Then she will cross over to Crinone.	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 100%	10 100%	20 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	1 10%	2 10%
Not Hispanic or Latino	9 90%	8 80%	17 85%
Unknown or Not Reported	0 0%	1 10%	1 5%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Female Change in Progesterone
Description	The primary outcome variables will be: the change in serum progesterone levels increase after coitus in the female partner using vaginal progesterone gel compared to placebo
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Vaginal Gel	Crinone Vaginal Progesterone Gel
Arm/Group Description	The couple will be given a prefilled applicator containing either Crinone gel (progesterone) or placebo vaginal gel, data collection sheets and laboratory requisitions. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Placebo vaginal gel: Placebo vaginal gel is inserted in the female vagina using the pre-filled applicator.	Crinone is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system containing a water swellable but insoluble polymer, polycarbophil. Crinone 8% is formulated to provide a long-acting vaginal retention, and is prescribed daily. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg of progesterone. The reported time to maximum progesterone concentration is 6.8 +/- 3.3 hours with use of a single dose of Crinone 8%. Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Crinone vaginal progesterone gel: Crinone vaginal progesterone gel is inserted in the female vaginal using the pre-filled applicator.
Measure Participants	20	20
Mean (Full Range) [ng/ml]	0.8	7.0

2. Secondary Outcome

Title	Male Change in Progesterone
Description	The secondary outcome variable will be the change in serum progesterone levels after coitus in the male partner comparing vaginal progesterone gel and placebo.
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Vaginal Gel	Crinone Vaginal Progesterone Gel
Arm/Group Description	The couple will be given a prefilled applicator containing either Crinone gel (progesterone) or placebo vaginal gel, data collection sheets and laboratory requisitions. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Placebo vaginal gel: Placebo vaginal gel is inserted in the female vagina using the pre-filled applicator.	Crinone is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system containing a water swellable but insoluble polymer, polycarbophil. Crinone 8% is formulated to provide a long-acting vaginal retention, and is prescribed daily. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg of progesterone. The reported time to maximum progesterone concentration is 6.8 +/- 3.3 hours with use of a single dose of Crinone 8%. Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Crinone vaginal progesterone gel: Crinone vaginal progesterone gel is inserted in the female vaginal using the pre-filled applicator.
Measure Participants	20	20
Mean (Full Range) [ng/ml]	0.54	0.85

Adverse Events

Time Frame	1 year
Arm/Group Title	Placebo Vaginal Gel		Crinone Vaginal Progesterone Gel
Arm/Group Description	The couple will be given a prefilled applicator containing either Crinone gel (progesterone) or placebo vaginal gel, data collection sheets and laboratory requisitions. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Placebo vaginal gel: Placebo vaginal gel is inserted in the female vagina using the pre-filled applicator.		Crinone is a bioadhesive vaginal gel containing micronized progesterone in an emulsion system containing a water swellable but insoluble polymer, polycarbophil. Crinone 8% is formulated to provide a long-acting vaginal retention, and is prescribed daily. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg of progesterone. The reported time to maximum progesterone concentration is 6.8 +/- 3.3 hours with use of a single dose of Crinone 8%. Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes. On the evening of day 3, the female will insert the applicator into the vagina, administer the gel, and have intercourse within 1 hour of insertion of the cream. Crinone vaginal progesterone gel: Crinone vaginal progesterone gel is inserted in the female vaginal using the pre-filled applicator.
All Cause Mortality
	Placebo Vaginal Gel		Crinone Vaginal Progesterone Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Vaginal Gel		Crinone Vaginal Progesterone Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Vaginal Gel		Crinone Vaginal Progesterone Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.