Although the postmenopausal ovary remains an important source of testo
sterone (T) production, there is nevertheless a decline in total circu
lating androgen levels with age. A role for androgen replacement in ad
dition to estrogens in some postmenopausal, particularly ovariectomize
d, women is increasingly gaining acceptance. We have compared the phar
macokinetics of two existing testosterone preparations, oral testoster
one undecanoate (TU) and sc testosterone implants, with a new matrix t
ransdermal delivery system for T. In study 1, three different doses of
TU (40 mg, two 20-mg doses 6 h apart and two 10-mg doses 6 h apart, o
rally) were investigated in 10 postmenopausal women. Median peak: leve
ls of 18 nmol/L (range, 5.8-64.0 nmol/L; 40 mg), 12.3 nmol/L (range, 5
.7-29.2 nmol/L; 20 mg), and 9.7 nmol/L (range, 7.8-28.7 nmol/L; 10 mg)
were observed, but T levels varied considerably within and between su
bjects regardless of the dose used. In study 2, 30 women receiving sc
estradiol therapy were randomized to receive either a 100-mg T implant
or placebo. In the T-treated group, levels peaked at 8.9 +/- 1.7 nmol
/L 1 month after insertion and then declined gradually to 2.9 +/- 0.4
nmol/L at 6 months. In study 3, a novel matrix transdermal delivery sy
stem for T was investigated in 6 females. Estimated daily delivery rat
es of 840 (TD1), 1100 (TD2), and 3000 mu g (TD3) T/24 h were investiga
ted. T rose rapidly after a single application of TD1 and TD2 and were
relatively constant for the next 18 h, at which time peaks of 2.3 +/-
1.0 and 4.1 +/- 1.6 nmol/L, respectively, at 24 h were seen. T concen
trations fell to baseline levels within 6 h after patch removal. When
TD2 was applied for 7 days, a T level of 4.3 +/- 0.7 nmol was seen 24
h after application, falling gradually to 2.8 +/- 0.7 nmol/L by day 7.
During twice weekly application of TD2, stable T concentrations were
maintained, and all peak levels were similar (peak level, 4.2 +/- 0.3
nmol/L 24 h post-TD application) as were predose troughs (3.2 +/- 0.3
nmol). Twice weekly application of TD3 produced a similar pattern of T
, and the mean peak and trough levels were 7.5 +/- 0.9 and 4.0 +/- 0.4
nmol/L, respectively. In conclusion, TU produced inappropriate high T
levels at all doses, with wide variations between subjects, confirmin
g that TU is unpredictably absorbed and unlikely to be satisfactory fo
r use in women. Subcutaneous testosterone implants produce unphysiolog
ical T levels for at least 1-2 months. The transdermal matrix delivery
system maintained relatively stable T levels within narrow ranges wit
h Little within- and between-subject variation. We conclude that such
transdermal systems may be of value for androgen therapy in postmenopa
usal women because they provide a highly controllable way of deliverin
g T noninvasively and reliably, and achieve mean physiological levels
not possible with existing methods.