Biomedical subjects

Susan R Davis

Publications and source records attributed to Susan R Davis.

43 records · Page 3Linked to original sources

PubMedDate not supplied

Transition from estrogen therapy to raloxifene in postmenopausal women: effects on treatment satisfaction and the endometrium-a pilot study.

OBJECTIVE: To compare the effects of transferring from low-dose, transdermal estrogen to raloxifene with a phase of alternate-day raloxifene therapy with or without low-dose transdermal estrogen on patient satisfaction, endometrial changes, and overall safety in healthy, postmenopausal women previously administered hormone therapy. DESIGN: Healthy postmenopausal women were randomized to one of two treatment groups: raloxifene + low-dose, transdermal estrogen (RLX+E) and raloxifene + placebo (RLX+P). The study consisted of four equal phases of 8 weeks each: Phase I (low-dose, transdermal estrogen, 25 microg/day), phase II (double-blind, alternate-day raloxifene 60 mg + low-dose, transdermal estrogen or placebo patch), phase III (alternate-day RLX 60 mg + placebo patch), and phase IV (raloxifene 60 mg/day + placebo patch). Primary endpoints included patient satisfaction, endometrial changes, overall safety, and quality of life. RESULTS: Sixty women were randomized in this study. Baseline characteristics were similar between the two treatment groups. For the primary analysis (phase II to phase IV, inclusive), there were no significant differences between the therapy sequences for patient satisfaction, endometrial thickness, or quality of life. In the therapy comparison phase (phase II), mean change in patient satisfaction score was 3.2 mm (SD = 16.2) for RLX+E and -17.1 mm (SD = 38.7) for RLX+P (P = 0.003), whereas mean change in endometrial thickness was 0.8 mm (SD = 2.7) for RLX+E and -0.9 mm (SD = 1.5) for RLX+P (P = 0.021). The RLX+P group showed a significantly greater increase in vasomotor events, with a mean score change of 1.7 (SD = 1.9) compared with a mean score change of 0.2 (SD = 1.8) in the RLX+E group (P = 0.005). There were no statistically significant differences between the two therapy groups in the reporting of treatment-emergent adverse events. CONCLUSION: Gradual conversion to raloxifene from low-dose estrogen, with a progression from 60 mg every alternate day to 60 mg/day, is a viable option in potentially symptomatic, postmenopausal women.

Administration, Cutaneous↗

PubMedDate not supplied

Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial.

OBJECTIVE: The extent to which aromatization of testosterone (T) to estradiol is required for the observed effects of testosterone therapy on sexual function and well-being are not known. Therefore, the authors investigated the effects of aromatase enzyme inhibition on sexual function, well-being, and mood in estrogen- and T-replete postmenopausal women in a double-blind, randomized, placebo-controlled study. DESIGN: Postmenopausal women using transdermal estrogen therapy for at least 8 weeks and reporting low sexual satisfaction (score <42 for the Sabbatsberg Sexual Self-rating Scale [SSS]) with a total T value of less than 1.2 nmol/L were treated with 400 muL of a 0.5% T gel (total dose 2 mg) and were randomly assigned to receive treatment with either 2.5 mg/day of letrozole or an identical placebo tablet. Women were assessed at baseline (week -2) and at 0, 4, 8, and 16 weeks. Sexual function was assessed with the SSS, well-being was assessed with the Psychological General Well-being Index, and mood was assessed with the Beck Depression Inventory at 0 and 16 weeks. Eighty-one women were screened, 76 were randomly assigned to a treatment group, and 30 in each group completed the study. Because this was a mechanistic study, only the 60 women who completed the study per protocol were included in the final analysis. RESULTS: Total T and calculated free T increased from baseline in both groups, with no difference between groups. At 16 weeks, estradiol, sex hormone-binding globulin, fasting lipids, lipoprotein(a), and C-reactive protein did not differ from baseline or between groups. Significant increases in total Sabbatsberg Sexual Self-rating Scale scores, total Psychological General Well-being Index scores, and a reduction in Beck Depression Inventory scores from baseline to 16 weeks was seen for both treatment groups, with no effect of treatment allocation. No adverse treatment effects were reported. CONCLUSIONS: Increases in total and free T in the physiologic range in postmenopausal women were associated with improved sexual satisfaction, well-being, and mood. In this study, aromatase inhibition did not influence any of these outcomes. Short-term transdermal T therapy did not modify fasting lipids, lipoprotein(a), or C-reactive protein.

Administration, Cutaneous↗

PubMedDate not supplied

Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial.

OBJECTIVE: Evaluation of the use of testosterone therapy for hypoactive sexual desire disorder (HSDD) after oophorectomy has mostly involved women treated with oral estrogen preparations. We investigated the efficacy and safety of a testosterone patch in surgically menopausal women receiving concurrent transdermal estrogen. DESIGN: Women with HSDD after oophorectomy, for whom this was a concern, who were using transdermal estrogen, were recruited to a 24-week, randomized, double-blind, placebo-controlled trial in Europe and Australia. Patients were randomly allocated to placebo (n = 40) or testosterone 300 microg/day (n = 37) treatment. Primary endpoints were changes in sexual desire measured by the sexual desire domain of the Profile of Female Sexual Function and the frequency of satisfying sexual activity at 24 weeks. RESULTS: Sixty-one women (79%) completed the trial. All subjects who received at least one application of study medication were included in analysis. The testosterone-treated group experienced a significantly greater change from baseline in the domain sexual desire score compared with placebo (change from baseline, 16.43 versus 5.98; P = 0.02). The domain scores for arousal, orgasm, decreased sexual concerns, responsiveness, and self-image as well as decreased distress were also significantly greater with testosterone therapy than placebo. The frequency of satisfactory sexual events increased but was not statistically different between treatment groups (P = 0.06) Adverse events occurred with similar frequency in both groups, and no serious risks of therapy were observed CONCLUSIONS: In this study, transdermal testosterone therapy via a skin patch improved sexual desire and other sexual function domains. It was well tolerated in these oophorectomized women with HSDD receiving concomitant transdermal estrogen.

Administration, Cutaneous↗

PubMedDate not supplied

Endogenous androgen levels and well-being: differences between premenopausal and postmenopausal women.

OBJECTIVE: We investigated whether there is a relationship between androgens levels and well-being in pre- and postmenopausal women. DESIGN: We randomly recruited 1423 women aged 18 to 75 years from the community via the electoral roll. Each provided a morning blood sample and completed the Psychological General Well Being Index questionnaire on the same day. Women were excluded if they took medication for any psychiatric illness, had abnormal thyroid function, or had documented polycystic ovarian syndrome. Analysis was by linear regression for well-being, including demographic and lifestyle variables as well as serum levels of androgens. RESULTS: We included 1224 women in the analysis. Being partnered was positively associated with well-being in premenopausal women. In postmenopausal women, well-being was positively related to age and exercising, whereas smoking, obesity, and postmenopausal hormone therapy use were each negatively associated with well-being. None of the measured androgens (total and free testosterone, dehydroepiandrosterone sulfate, and androstenedione) made an independent contribution to well-being in postmenopausal women (n = 603). However, for premenopausal women (n = 621), levels of dehydroepiandrosterone sulfate were independently and positively associated with the domain score for vitality. CONCLUSIONS: Our findings do not support an important independent role for androgens as determinants of well-being in postmenopausal women. That dehydroepiandrosterone sulfate alone is associated with greater vitality in premenopausal women is of interest but requires further evaluation as an a priori hypothesis in another study.

Adolescent↗

PubMedDate not supplied

Testosterone aromatization and cognition in women: a randomized, placebo-controlled trial.

OBJECTIVE: To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy, estrogen-treated postmenopausal women. DESIGN: Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks, with a serum total testosterone less than 1.2 nmol/L participated in a single-center, double-blind, randomized, placebo-controlled study. All participants received transdermal testosterone, 400 muL of a 0.5% testosterone gel, daily and were randomized to receive either letrozole 2.5 mg/day or an identical placebo tablet. The main outcome measure was cognition, evaluated using a comprehensive battery of standardized neuropsychological tests, at baseline and week 16. RESULTS: Thirty women in each group completed the study. Free testosterone increased from baseline in both groups, with no difference between groups. Free testosterone levels achieved were below the 90th centile for young women in 80% of the participants at week 16. Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study. No clinically significant effects of testosterone treatment were seen for attention and working memory, psychomotor speed, or executive function. Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy, all of which were unaffected by the aromatase inhibitor. CONCLUSIONS: We did not observe any effects of aromatase inhibition on cognition in healthy, estrogen-treated postmenopausal women treated with testosterone. This may be due to insufficient study power or a true lack of effect. However, our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large randomized, controlled trials.

Administration, Cutaneous↗

PubMedDate not supplied

Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study.

OBJECTIVE: To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 microg/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24). RESULTS: A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels < or = 160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels < or = 160 nmol/L, mean change of 2.1 +/- 0.28 versus 0.5 +/- 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 +/- 0.26 versus 0.5 +/- 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated. CONCLUSIONS: Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder.

Administration, Cutaneous↗

PubMedDate not supplied

Endogenous androgen levels and cardiovascular risk profile in women across the adult life span.

OBJECTIVE: Whether endogenous androgen levels contribute to the cardiovascular disease (CVD) risk profile in women is controversial. The purpose of this study was to investigate systematically the relationships between serum levels of endogenous androgens and sex hormone-binding globulin (SHBG) and biochemical CVD risk profile, taking other known risk factors into account. DESIGN: This community-based cross-sectional study included 587 non-healthcare-seeking-women, aged 18 to 75 years, who were randomly recruited from the community via the electoral roll from April 2002 to August 2003. Participants were euthyroid; had no usage of exogenous steroids; had no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and did not have hyperprolactinemia or polycystic ovarian syndrome. The relationships between total testosterone, SHBG, free testosterone, dehydroepiandrosterone sulfate, and androstenedione and high-sensitivity C-reactive protein (CRP) and lipids were explored using linear regression with natural logarithm (ln) -or square root-transformed data as indicated. Issues of nonlinearity and interaction were addressed by the inclusion of extra regression terms where appropriate. We determined the change in the proportion of variation for each marker of the CVD risk profile explained by the addition of each hormone term to the models, having adjusted for age, body mass index, smoking, alcohol, and exercise. RESULTS: Menopausal status did not influence the statistical models for high-sensitivity CRP and high-density lipoprotein cholesterol, but for both low-density lipoprotein cholesterol and triglycerides, the proportion of variation explained by the models was substantially less in postmenopausal than in premenopausal women. Almost all of the highly statistically significant findings were related to the addition of the SHBG terms to the models. The changes in r2 values were highly statistically significant for the addition of the SHBG terms to the models for ln CRP and ln high-density lipoprotein for both pre- and postmenopausal women (P <= 0.01 and < 0.001, respectively) and for ln triglycerides in postmenopausal (P < 0.001) and premenopausal women (P < 0.01). CONCLUSIONS: Endogenous testosterone and the adrenal preandrogens per se are not significant independent determinants of circulating high-sensitivity CRP or lipoprotein lipids. Our analyses provide further support for the independent predictive value of low SHBG levels for CVD risk profile and an independent contribution of the menopausal transition to the determination of low-density lipoprotein cholesterol and triglycerides.

Adolescent↗