Sonia Davison | PubMed Health

PubMed2005

Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women.

This was a preliminary feasibility study to assess the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system in postmenopausal women. Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose of testosterone (0.1, 0.2, or 0.3 mg) by inhalation. Plasma concentrations of sex steroids were measured between 1 and 360 minutes. Pulmonary and cardiovascular adverse events were monitored. Inhaled testosterone produced a dose-dependent increase in plasma total and free testosterone. At the highest dose (0.3 mg), total and free testosterone increased from baseline (mean +/- SD, 0.6 +/- 0.3 nmol/L, 2.5 +/- 1.0 pmol/L) to maximum levels of 62.6 +/- 20.4 nmol/L (total) and 168.2 +/- 50.2 pmol/L(free), occurring 1 to 2 minutes after dosing. A 2-compartment model best described the free and total testosterone pharmacokinetic profile. Dihydrotestosterone levels were higher than baseline at 60 minutes (P < .0002). Estradiol did not vary, but sex hormone binding globulin and albumin fell. There were no adverse events related to the treatment. Administration of inhaled testosterone is safe and achieves a supraphysiologic "pulse" kinetic profile of total and free testosterone with a rapid return to pretreatment levels.

Administration, Inhalation↗

PubMed2003

Hormone replacement therapy: current controversies.

Postmenopausal hormonal therapy is used to manage the climacteric symptoms that impair the quality of life of a substantial number of women. The difficulty is achieving the desired effects with minimal side-effects and no adverse health risks. Fundamental to this is understanding the physiology of oestrogen in women and the metabolism of the therapeutic compounds. Although the effects of oral oestrogen therapy have been studied extensively, there is insufficient evidence to assess adequately the independent effects of progestin use, other oestrogen compounds, differing doses and duration of treatment. We have reviewed some basic concepts of oestrogen physiology and how these relate to exogenous oestrogen administration, the risks of greatest concern, and the role of androgens and newer treatment alternatives.

Aged↗

PubMed2003

New markers for cardiovascular disease risk in women: impact of endogenous estrogen status and exogenous postmenopausal hormone therapy.

The role of estrogen in altering cardiovascular disease risk in women is contentious. Menopause is associated with increased risk for ischemic heart disease and cerebrovascular disease, which collectively are the main causes of morbidity and mortality in women of developed nations. Observational studies suggest a protective role of estrogen, whereas recent randomized controlled trials report a negative role for oral estrogen in primary and secondary prevention of cardiovascular events. Inflammatory mechanisms underlie the process of arterial thrombus formation following atheromatous plaque rupture, and as such modulation of the inflammatory process may be a potential means of reducing cardiovascular risk. Sex steroids may influence inflammatory processes and hence modify cardiovascular risk. The objective of the study was to review the current understanding of the relationships between C-reactive protein (CRP), homocysteine, IL-6, and lipoprotein (a) [Lp(a)] and endogenous estrogen status, exogenous estrogen treatment, and cardiovascular disease risk. The design was a review of all relevant published, peer- reviewed studies. Raised levels of CRP, homocysteine, Lp(a), IL-6, and CRP are each independently associated with increased risk for cardiovascular events in women. Changes in these parameters across the menopausal transition cannot clearly be attributed to hormonal changes. With respect to the effects of exogenous postmenopausal therapy, oral estrogen use is consistently associated with elevations in CRP, no change or a reduction in homocysteine, varied effects on IL-6, and a consistent reduction in Lp(a). Transdermal estradiol overall has no significant effect on any of these parameters. Progestin use appears to attenuate the effect of oral estrogen on CRP and is associated with a reduction in Lp(a). Like oral estrogen, tibolone use is associated with a rise in CRP, with no change in homocysteine and consistent lowering of Lp(a). Selective estrogen receptor modulators modestly lower homocysteine and Lp(a), have varied effects on CRP, and have no reported effects on IL-6. Despite these varied effects of postmenopausal hormone treatment on inflammatory markers, homocysteine, and Lp(a), there is no evidence that change in these markers results in modification of cardiovascular risk. Further studies are required to specifically investigate whether treatments that increase or decrease these markers in fact modulate the risk of cardiovascular events in women.

Biomarkers↗