Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men.
BACKGROUND
Testosterone (T) plus progestin combinations are the most promising hormonal male contraceptives. Nestorone (NES), a progestin without estrogenic or androgenic activity, when combined with T may be an excellent candidate for male contraception.


OBJECTIVE
Our objective was to determine the effect of transdermal NES gel alone or with T gel on gonadotropin suppression.


METHODS
The randomized, unblinded clinical trial was conducted at two academic medical centers.


METHODS
A total of 140 healthy male volunteers participated.


METHODS
One hundred subjects were randomized initially (20 per group) to apply NES gel 2 or 4 mg, T gel 10 g, or T gel 10 g plus NES gel 2 or 4 mg daily for 20 d. Because only about half of the subjects in T plus NES 4 mg group suppressed serum gonadotropins to 0.5 IU/liter or less (suboptimal suppression), two additional groups of 20 men were randomized to apply daily T gel 10 g plus NES gel 6 or 8 mg.


METHODS
Suppression of serum LH and FSH concentrations to 0.5 IU/liter or less after treatment was the main outcome variable.


RESULTS
A total of 119 subjects were compliant with gel applications with few study-related adverse events. NES alone reduced gonadotropins significantly but less than T gel alone. Combined T gel 10g plus NES gel 6 or 8 mg suppressed both serum gonadotropins to 0.5 IU/liter or less in significantly more men than either gel alone.


CONCLUSIONS
Transdermal NES gel alone had gonadotropin suppression activity. Combined transdermal NES (6 or 8 mg) plus T gel demonstrated safe and effective suppression of gonadotropins, justifying a longer-term study of this combination for suppression of spermatogenesis.
Department of Medicine, Division of Endocrinology, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509, USA.
Vahid
V
Mahabadi
John K
JK
Amory
Ronald S
RS
Swerdloff
William J
WJ
Bremner
Stephanie T
ST
Page
Regine
R
Sitruk-Ware
Peter D
PD
Christensen
Narender
N
Kumar
Yun-Yen
YY
Tsong
Diana
D
Blithe
Christina
C
Wang
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D003267:Contraception / Q000009:adverse effects / Q000379:methods*; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D005782:Gels / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009653:Norprogesterones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
D003272:Contraceptive Agents, Male; D004338:Drug Combinations; D005782:Gels; D006062:Gonadotropins; D009653:Norprogesterones; D045167:Progesterone Congeners; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; C029167:ST 1435