Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men.
Adolescent
Adult
Contraceptive Agents, Hormonal
/ pharmacokinetics
Contraceptive Agents, Male
/ pharmacokinetics
Double-Blind Method
Drug Combinations
Follicle Stimulating Hormone
/ blood
Gonadotropins
/ blood
Hormonal Contraception
Humans
Luteinizing Hormone
/ blood
Male
Middle Aged
Norprogesterones
/ pharmacokinetics
Sperm Count
Spermatogenesis
/ drug effects
Surveys and Questionnaires
Testosterone
/ pharmacokinetics
Testosterone Congeners
/ pharmacology
Young Adult
gonadotropins
male hormonal contraception
nestorone
progestin
testosterone
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
25
11
2018
revised:
31
01
2019
accepted:
01
02
2019
pubmed:
11
4
2019
medline:
4
8
2020
entrez:
11
4
2019
Statut:
ppublish
Résumé
Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups. We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment. Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels. Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.
Sections du résumé
BACKGROUND
Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone
OBJECTIVE
Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups.
DESIGN
We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment.
RESULTS
Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels.
CONCLUSION
Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.
Identifiants
pubmed: 30969032
doi: 10.1111/andr.12603
pmc: PMC6768743
mid: NIHMS1011244
doi:
Substances chimiques
Contraceptive Agents, Hormonal
0
Contraceptive Agents, Male
0
Drug Combinations
0
Gonadotropins
0
Norprogesterones
0
Testosterone Congeners
0
Testosterone
3XMK78S47O
ST 1435
7759-35-5
Luteinizing Hormone
9002-67-9
Follicle Stimulating Hormone
9002-68-0
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
878-887Subventions
Organisme : NICHD NIH HHS
ID : HHSN275201200002I
Pays : United States
Organisme : NICHD NIH HHS
ID : K23 HD073164
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275200403369I
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR000122
Pays : United States
Organisme : NICHD Contraceptive Discovery and Development Branch
ID : HHSN275201300024
Pays : International
Organisme : UCLA Clinical and Translational Science Institute at Harbor-UCLA Medical Center
Pays : International
Organisme : NIDDK NIH HHS
ID : T32 DK007571
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201300024I
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD042454
Pays : United States
Organisme : Population Council
Pays : International
Organisme : NICHD NIH HHS
ID : HHSN275201200002C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201300025I
Pays : United States
Organisme : NICHD Contraceptive Discovery and Development Branch
ID : HHSN275201200002
Pays : International
Informations de copyright
© 2019 American Society of Andrology and European Academy of Andrology.
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