This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buckler, H. M. Articles by Wu, F. C. W. Search for Related Content PubMed PubMed Citation Articles by Buckler, H. M. Articles by Wu, F. C. W.

Which Androgen Replacement Therapy for Women?¹

Department of Endocrinology and Medicine, University of Manchester, Hope Hospital (H.M.B., W.R.R.), Salford, United Kingdom M6 8HD; and Manchester Royal Infirmary (F.C.W.W.), Manchester, United Kingdom M13 9PL

Address all correspondence and requests for reprints to: Dr. H. M. Buckler, Department of Endocrinology and Medicine, University of Manchester, Hope Hospital, Eccles Old Road, Salford, United Kingdom M6 8HD.

Although the postmenopausal ovary remains an important source of testosterone (T) production, there is nevertheless a decline in total circulating androgen levels with age. A role for androgen replacement in addition to estrogens in some postmenopausal, particularly ovariectomized, women is increasingly gaining acceptance. We have compared the pharmacokinetics of two existing testosterone preparations, oral testosterone undecanoate (TU) and sc testosterone implants, with a new matrix transdermal 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, orally) were investigated in 10 postmenopausal women. Median peak levels 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 subjects 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 system for T was investigated in 6 females. Estimated daily delivery rates of 840 (TD1), 1100 (TD2), and 3000 µg (TD3) T/24 h were investigated. 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 concentrations 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, confirming that TU is unpredictably absorbed and unlikely to be satisfactory for use in women. Subcutaneous testosterone implants produce unphysiological T levels for at least 1–2 months. The transdermal matrix delivery system maintained relatively stable T levels within narrow ranges with little within- and between-subject variation. We conclude that such transdermal systems may be of value for androgen therapy in postmenopausal women because they provide a highly controllable way of delivering T noninvasively and reliably, and achieve mean physiological levels not possible with existing methods.

This article has been cited by other articles:

				F. Fabregues, J. Penarrubia, M. Creus, D. Manau, G. Casals, F. Carmona, and J. Balasch Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial Hum. Reprod., February 1, 2009; 24(2): 349 - 359. [Abstract] [Full Text] [PDF]

				J. Balasch, F. Fabregues, J. Penarrubia, F. Carmona, R. Casamitjana, M. Creus, D. Manau, G. Casals, and J. A. Vanrell Pretreatment with transdermal testosterone may improve ovarian response to gonadotrophins in poor-responder IVF patients with normal basal concentrations of FSH Hum. Reprod., July 1, 2006; 21(7): 1884 - 1893. [Abstract] [Full Text] [PDF]

				W. Arlt Androgen therapy in women Eur. J. Endocrinol., January 1, 2006; 154(1): 1 - 11. [Abstract] [Full Text] [PDF]

				L.M. Rivera-Woll, M. Papalia, S.R. Davis, and H.G. Burger Androgen insufficiency in women: diagnostic and therapeutic implications Hum. Reprod. Update, September 1, 2004; 10(5): 421 - 432. [Abstract] [Full Text] [PDF]

				K. K. Miller Androgen Deficiency in Women J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2395 - 2401. [Abstract] [Full Text] [PDF]

				C. V. Obiezu, E. J. Giltay, A. Magklara, A. Scorilas, L. J.G. Gooren, H. Yu, D. J.C. Howarth, and E. P. Diamandis Serum and Urinary Prostate-specific Antigen and Urinary Human Glandular Kallikrein Concentrations Are Significantly Increased after Testosterone Administration in Female-to-Male Transsexuals Clin. Chem., June 1, 2000; 46(6): 859 - 862. [Abstract] [Full Text] [PDF]

				S. Davis Androgen Replacement in Women: A Commentary J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1886 - 1891. [Abstract] [Full Text]