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Biomedical subjects

Susan R Davis

Publications and source records attributed to Susan R Davis.

At least 19 recordsLinked to original sources
PubMed2007

DHEA therapy for women: effect on sexual function and wellbeing.

DHEA is increasingly available commercially as a supplement aimed at improving libido and wellbeing in postmenopausal women. However there is scant evidence to support the use of DHEA for this purpose, and safety data for DHEA therapy are lacking. Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most abundant circulating sex steroid hormones in women, providing a large precursor reservoir for the intracellular production of androgens and oestrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been proposed that restoring the circulating levels of these steroids to those found in young people may have anti-ageing effects and improve wellbeing and sexual function. However this is not supported by the published literature. We have reviewed the physiology of DHEA and DHEAS in women and the published literature pertaining to the use of DHEA therapy for libido and wellbeing in postmenopausal women. The literature was searched using Medline (Ovid) and Pub-Med for original studies. Overall, the interpretation of data from randomised controlled trials conducted in well women is limited by inadequate sample size and short treatment durations with inconsistent results for the outcomes of libido and wellbeing. Studies of DHEA in women with adrenal insufficiency, although indicating potential improvements in mood and libido, are also limited by their short treatment phase durations. In addition safety data for DHEA therapy are lacking. The potential value of DHEA therapy for women still requires exploration in adequately powered well-designed randomised placebo-controlled trials. The studies of DHEA therapy in women with adrenal insufficiency suggest that this group is the most likely to derive health benefits from DHEA supplementation.

Adjuvants, Immunologic↗
PubMed2006

Androgen therapy in women: an Endocrine Society Clinical Practice guideline.

OBJECTIVE: The objective was to provide guidelines for the therapeutic use of androgens in women. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. EVIDENCE: The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group. The strength of a recommendation is indicated by the number 1 (strong recommendation, associated with the phrase "we recommend") or 2 (weak recommendation, associated with the phrase "we suggest"). The quality of the evidence is indicated by cross-filled circles, such that [1 cross-filled circle, 3 empty circles] denotes very-low-quality evidence, [2 cross-filled circles, 2 empty circles] low quality, [3 cross-filled circles, 1 empty circle] moderate quality, and [4 cross-filled circles] high quality. Each recommendation is followed by a description of the evidence. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the task force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Committee (CAC), and Executive Committee. The version approved by the CGS and CAC was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: We recommend against making a diagnosis of androgen deficiency in women at present because of the lack of a well-defined clinical syndrome and normative data on total or free testosterone levels across the lifespan that can be used to define the disorder. Although there is evidence for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, we recommend against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking. A review of the data currently available is presented, and areas of future research are outlined. To formulate clinical guidelines for use of testosterone in women, additional information will be necessary. This includes defining conditions that, when not treated with androgens, have adverse health consequences to women; defining clinical and laboratory parameters that distinguish those with these conditions; and assessing the efficacy and long-term safety of androgen administration on outcomes that are important to women diagnosed with these conditions. This necessary clinical research cannot occur until the biological, physiological, and psychological underpinnings of the role of androgens in women and candidate disorders are further elucidated.

Affect↗
PubMed2006

Comparison of effects of pravastatin and hormone therapy on soluble P-selectin and platelet P-selectin expression in postmenopausal hypercholesterolemic women.

OBJECTIVE: Recent trials have suggested an adverse early effect on cardiovascular risk of hormone therapy (HT) in postmenopausal women, an effect which could be due to an increase in arterial thrombosis via platelet activation. We examined the effect of HT on platelet surface expression of P-selectin, a marker of platelet activation, and plasma levels of soluble P-selectin, also believed to be a marker of platelet activation, and compared these effects with pravastatin, a drug proven to reduce cardiovascular events and reported to decrease both platelet and soluble P-selectin. METHODS: Surface expression of platelet P-selectin, soluble P-selectin and fasting lipids were measured at baseline and 6 months in a randomized, double-blind study of postmenopausal hypercholesterolemic women comparing low-dose combined HT (1mg estradiol + 0.5 mg norethisterone acetate; n = 26) with pravastatin (n = 24). RESULTS: After adjusting for baseline levels, HT and pravastatin produced similar reductions in soluble P-selectin (p < 0.0001 for both). The percentage of platelets expressing P-selectin was also reduced by pravastatin (p = 0.025), but there was a trend to an increase in platelet P-selectin expression with HT (p = 0.13), and a significant difference between pravastatin and HT in the changes in platelet P-selectin (p < 0.002). No relationship was evident between changes in soluble or platelet P-selectin and changes in lipids with either treatment. CONCLUSIONS: In postmenopausal hypercholesterolemic women, both pravastatin and HT reduced soluble P-selectin levels, but only pravastatin reduced P-selectin expression on the surface of platelets. An implication of these findings is that the reduction in soluble P-selectin by HT may occur by a non-platelet related mechanism.

Aged↗
PubMed2006

Determinants of change in patella cartilage volume in healthy subjects.

OBJECTIVE: To examine whether the amount of patella cartilage in healthy, middle-aged subjects is stable or changes over time, and what factors may influence the changes. METHODS: Eighty-five subjects (28 men and 57 women, mean age 55.5 yrs) had magnetic resonance imaging of their dominant knee at baseline and 2 years later. Patella and tibial cartilage volume was measured at baseline and followup. Risk factors assessed at baseline were tested for their association with change in patella cartilage volume over time. RESULTS: Mean annual percentage loss of patella cartilage was 2.1 (95% confidence interval: 1.1-3.2; p < 0.001). Age, gender, body mass index, and initial cartilage volume did not affect rate of change of patellar cartilage volume. There was a weak association between change in patellar cartilage volume and change in lateral tibial cartilage volume (R = 0.23, p = 0.03) but not medial tibial cartilage volume (R = 0.09, p = 0.43). CONCLUSION: In healthy subjects, a significant amount of patella cartilage is lost annually. The poor correlation between patella and tibial cartilage loss suggests that pathogenetic mechanisms for osteoarthritis in the patellofemoral and tibiofemoral joint may differ. Further work will be required to determine whether the rate of patella cartilage loss in healthy subjects is steady or phasic, and to determine which factors can be modified to reduce cartilage loss.

Aging↗
PubMed2006

The relationship between the knee adduction moment and knee pain in middle-aged women without radiographic osteoarthritis.

OBJECTIVE: . An abnormally high knee adduction moment increases the medial tibiofemoral compartment load at the knee during gait, and is an important biomechanical marker of joint pathology. This cross-sectional study examines the relationship between the knee adduction moment and knee pain in middle-aged women without radiographic knee osteoarthritis (OA). METHODS: Three-dimensional Vicon gait analyses were performed on 20 women who had knee pain but no radiological evidence of joint pathology. RESULTS: In multivariate analysis, the peak knee adduction moment during the late stance phase of gait was inversely associated with knee pain [beta: -10.1 (95% CI -17.6, -2.7), p = 0.01] after adjustment for body mass index (BMI) and age. This explained that the knee adduction moment during late stance contributed 32% of the variance in knee pain. The peak knee adduction moment during early stance was not significantly associated with knee pain prior to and after adjustment for BMI and age. CONCLUSION: There is a significant inverse association between the peak knee adduction moment during late stance and the amount of knee pain experienced by women without radiographic evidence of joint pathology. This may represent a compensatory mechanism to reduce medial tibiofemoral joint load in the setting of knee pain.

Arthralgia↗
PubMed2005

A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder.

We tested and compared the use of two adjunctive hormonal agents, tamoxifen and medroxyprogesterone acetate (MPA), for the treatment of acute mania or hypomania. A total of 13 women with acute Bipolar Affective Disorder in the manic or hypomanic phase were recruited from a clinical population to participate in this 28-day, three-arm, double blind, placebo-controlled study. The women who received tamoxifen exhibited significant improvement in symptoms of mania from baseline to final assessment compared with the placebo group. The MPA group improved more than the placebo group. Further exploration of tamoxifen as a useful adjunct in the treatment of acute manic symptoms in women with Bipolar Affective Disorder is warranted.

Acute Disease↗
PubMed2005

Differential expression of factors involved in fat metabolism with age and the menopause transition.

OBJECTIVES: Changes in the hormonal milieu at the menopause are associated with an increase in total adiposity and a more android pattern of fat distribution, with the latter associated with an increased risk of the metabolic syndrome. The aim of this study was to explore potential mechanisms that might contribute to the changes in body composition associated with the menopause transition. METHODS: Using real-time PCR analysis, we have compared the expression of various factors involved in fat metabolism in subcutaneous abdominal and gluteal fat in premenopausal (Group 1; n=11), postmenopausal (Group 2; n=10) and postmenopausal women taking estrogen therapy (Group 3; n=10). RESULTS: All subjects were of normal body mass index, euglycemic and normolipemic. The postmenopausal women were older (Group 1, 43.1+5.0 versus Groups 2 and 3, 57.9+/-7.4 years, P<0.001 and 56.1+/-4.5 years, P<0.001, respectively). Expression analysis revealed that levels of transcripts encoding adiponectin, peroxisome proliferator-activated receptor gamma and fatty acid transporter, each associated with insulin sensitivity, were significantly greater in gluteal fat from estrogen deplete postmenopausal women than in fat from the other two groups (P<0.05). In contrast, levels of transcripts for acetyl CoA carboxylase alpha, long chain acyl CoA dehydrogenase and hormone sensitive lipase were significantly greater in abdominal fat from premenopausal women than either postmenopausal groups (P<0.05). CONCLUSIONS: These findings indicate both aging and the menopause transition are associated with changes in fat metabolism, which may contribute to the accumulation of body fat after menopause.

Acetyl-CoA Carboxylase↗
PubMed2005

Circulating androgen levels and self-reported sexual function in women.

CONTEXT: It has been proposed that low sexual desire and sexual dysfunction are associated with low blood testosterone levels in women. However, evidence to support this is lacking. OBJECTIVE: To determine whether women with low self-reported sexual desire and sexual satisfaction are more likely to have low serum androgen levels than women without self-reported low sexual desire and sexual satisfaction. DESIGN, SETTING, AND PARTICIPANTS: A community-based, cross-sectional study of 1423 women aged 18 to 75 years, who were randomly recruited via the electoral roll in Victoria, Australia, from April 2002 to August 2003. Women were excluded from the analysis if they took psychiatric medication, had abnormal thyroid function, documented polycystic ovarian syndrome, or were younger than 45 years and using oral contraception. MAIN OUTCOME MEASURES: Domain scores of the Profile of Female Sexual Function (PFSF) and serum levels of total and free testosterone, androstenedione, and dehydroepiandrosterone sulfate. RESULTS: A total of 1021 individuals were included in the final analysis. No clinically significant relationships between having a low score for any PFSF domain and having a low serum total or free testosterone or androstenedione level was demonstrated. A low domain score for sexual responsiveness for women aged 45 years or older was associated with higher odds of having a serum dehydroepiandrosterone sulfate level below the 10th percentile for this age group (odds ratio [OR], 3.90; 95% confidence interval [CI], 1.54-9.81; P = .004). For women aged 18 to 44 years, having a low domain score for sexual desire (OR, 3.86; 95% CI, 1.27-11.67; P = .02), sexual arousal (OR, 6.39; 95% CI, 2.30-17.73; P<.001), and sexual responsiveness (OR, 6.59; 95% CI, 2.37-18.34; P<.001) was associated with having a dehydroepiandrosterone sulfate level below the 10th percentile. CONCLUSIONS: No single androgen level is predictive of low female sexual function, and the majority of women with low dehydroepiandrosterone sulfate levels did not have low sexual function.

Adolescent↗
PubMed2005

Intranasal versus transdermal matrix oestrogen replacement in Australasian women.

OBJECTIVES: To compare the efficacy and patient acceptability of intranasal and transdermal 17beta-oestradiol delivery systems for postmenopausal symptoms in Australasian women. METHODS: Symptomatic postmenopausal women were randomly assigned to treatment with either intranasal 17beta-oestradiol, 300 microg daily (n = 66) or transdermal matrix patch 17beta-oestradiol, 50 microg/day (n = 66) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the modified Greene climacteric scale, the menopause quality of life (MENQOL) questionnaire and vasomotor symptoms at week 12. Patient acceptability was compared by a satisfaction questionnaire at week 16 and patient preference at week 16. RESULTS: Intranasal and transdermal therapy produced significant reductions in both the Modified Greene and MENQOL scores, and in the occurrence of hot flushes and night sweats at week 12. The overall rate of reported vasomotor symptoms was lower on patients treated with the nasal spray. Both therapies were well tolerated with similar adverse event rates. Satisfaction and preference were similar for both modes of drug delivery. CONCLUSIONS: Intranasal oestradiol therapy route has comparable efficacy and safety to that of transdermal oestradiol matrix patch therapy with no difference in patient preference or satisfaction.

Administration, Cutaneous↗
PubMed2005

Measurement of total testosterone in women: comparison of a direct radioimmunoassay versus radioimmunoassay after organic solvent extraction and celite column partition chromatography.

OBJECTIVE: To evaluate the clinical usefulness for the measurement of testosterone (T) values in the "low" female range with a direct radioimmunoassay (RIA) for total T by comparing total T values measured by this assay with values determined by conventional RIA after organic solvent extraction/column chromatography. DESIGN: Cross-sectional study. SETTING: Victoria, Australia. PATIENT(S): Two hundred fifty-nine healthy women, aged 18-75 years, recruited from the community. INTERVENTION(S): Fasting serum samples were obtained and stored at -80 degrees C. MAIN OUTCOME MEASURE(S): Total T measurement. Total T was measured by the direct RIA method using antibody-coated tubes and iodine-labeled T tracer. For comparison, total T levels were also measured using the conventional RIA method after organic solvent (ethyl acetate:hexane [3:2]) extraction and celite column partition chromatography before RIA. RESULT(S): The mean T level by direct RIA was 0.76 nmol/L (median, 0.70; SD, 0.54; minimum, 0.10; maximum, 3.2). The mean difference between the two measurements (direct RIA - conventional RIA) was -0.28 (SD, 0.3). The direct RIA value was 63% (95% confidence interval, 26%-155%) of the conventional RIA estimate. For the classification of values at the lower end of the range, there was very good agreement beyond chance (kappa = 0.68-0.74) for values in approximately the lowest 10th-40th percentiles. CONCLUSION(S): The direct RIA is a clinically useful assay for the study of the issue of "low" T within the female population.

Adolescent↗
PubMed2005

Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy.

OBJECTIVE: Although natural menopause is associated with loss of ovarian estrogen production, this life phase is followed by a significant increase in estrogen-related cancers, namely breast and endometrial cancer. These tissues, as well as adipose, skeletal, and vascular tissues and the brain are important sites of postmenopausal estrogen production. Circulating C19 steroid precursors are essential substrates for extragonadal estrogen synthesis; however, the levels of these androgenic precursors decline markedly with advancing age. This implies an increase in capacity for extragonadal tissues to produce estrogen with age. DESIGN: To explore this, and the effects of the menopause transition and postmenopausal estrogen therapy on extragonadal estrogen biosynthesis, we have compared the expression of the aromatase gene and estrogen (ER) and androgen receptors (AR) in subcutaneous abdominal and gluteal fat taken from premenopausal (group 1: n = 11), postmenopausal (group 2: n = 10), and postmenopausal women taking estrogen therapy (group 3: n = 10). All subjects were of normal body mass index, euglycemic, and normolipemic. RESULTS: The postmenopausal women were older (group 1, 43.1 +/- 5.0 vs groups 2 and 3, 57.9 +/- 7.4 years, P < 0.001 and 56.1 +/- 4.5 years, P < 0.001, respectively) and had lower serum estradiol levels (group 2, 22.2 +/- 3.2 vs group 1, 442.5 +/- 248.2 pmol/L, P < 0.05), which were restored to premenopausal levels with estrogen therapy. Expression analysis revealed that levels of transcripts encoding aromatase were greater in gluteal than abdominal depots in each group in postmenopausal versus premenopausal women (P < 0.05). Use of hormone therapy did not influence aromatase gene expression in either depot. No differences were detected in the expression of ER or AR between groups of between tissue depots. CONCLUSION: Thus, the capacity of adipose tissue to produce estrogen seems to increase significantly with age at the time of menopause and to be unaltered by exogenous estrogen therapy. This difference in extragonadal estrogen production with age may play a pivotal role in the increase in estrogen-dependent malignancies in the postmenopausal years.

Adipose Tissue↗
PubMed2004

Postmenopausal testosterone therapy and breast cancer risk.

BACKGROUND: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen-progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. OBJECTIVE: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. DESIGN: Literature review. SETTING: The Jean Hailes Foundation, Research Unit. MAIN OUTCOME MEASURES: Mammary epithelial proliferation, apoptosis and breast cancer. RESULTS: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. CONCLUSION: Available data indicate the inclusion of testosterone in estrogen-progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting.

Animals↗
PubMed2004

Osteoarthritis and the postmenopausal woman: Epidemiological, magnetic resonance imaging, and radiological findings.

BACKGROUND: There is some observational evidence to suggest an effect of hormones on osteoarthritis (OA), especially in perimenopausal women. OBJECTIVES: To review the epidemiological evidence for an effect of estrogen replacement therapy (ERT) on the incidence and prevalence of OA, especially radiological OA, and the effect of ERT on articular cartilage in women. METHODS: The literature relating to these questions was reviewed using OVID Medline (1966 to March 2003). RESULTS: Some studies which have suggested a protective effect of ERT on the incidence and prevalence of OA. However, many of the confidence intervals include unity. Although a protective effect also was seen on articular knee cartilage in long-term users of ERT compared with never users, no difference in change in cartilage was seen over 2 years. CONCLUSIONS: There is weak epidemiological evidence suggesting a role for estrogen therapy in joint health in postmenopausal women. The data are more suggestive of an effect on large joint OA than small joint OA.

Arthrography↗
PubMed2004

Endocrine aspects of female sexual dysfunction.

INTRODUCTION: Various endogenous hormones, including estrogen, testosterone, progesterone and prolactin, may influence female sexual function. AIM: To provide recommendations for the diagnosis and treatment of women with endocrinologic sexual difficulties. METHODS: The Endocrine Aspects of Female Sexual Dysfunction Committee was part of a multidisciplinary International Consultation. It included four experts from two countries and several peer reviewers. MAIN OUTCOME MEASURE: Expert opinion was based on committee discussion, a comprehensive literature review and evidence-based grading of available publications. RESULTS: The impact of hormones on female sexual function and their etiological roles in dysfunction is complex. Research data are limited as studies have been hampered by lack of precise hormonal assays and validated measures of sexual function in women. Sex steroid insufficiency is associated with urogenital atrophy and may also adversely affect central sexual thought processes. Systemic estrogen/estrogen progestin therapy alleviates climacteric symptoms but there is no evidence that this therapy specifically improves hypoactive sexual desire disorder (HSDD) in premenopausal or postmenopausal women. Exogenous testosterone has been shown in small randomized controlled trials (RCT) to improve sexual desire, arousal and sexual satisfaction in both premenopausal and postmenopausal women. However, as there is no biochemical measure that clearly identifies who to treat, use of exogenous testosterone should be considered only after other causes of HSDD have been excluded, such as depression, relationship problems and ill health. The clinical assessment of HSDD should include detailed medical, gynecologic, sexual and psychosocial history and physical examination including the external/internal genitalia. Hormonal therapy should be individualized and risks/benefits fully discussed, and all treated women should be carefully followed up and monitored for therapeutic side effects. CONCLUSIONS: There is a need for prospective, multi-institutional clinical trials to define safe and effective endocrine treatments for female sexual dysfunction.

Age Factors↗
PubMed2004

Testosterone effects on the breast: implications for testosterone therapy for women.

Androgens have important physiological effects in women. Postmenopausal androgen replacement, most commonly as testosterone therapy, is becoming increasingly widespread. This is despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety data. With respect to the breast specifically, there is the potential for exogenous testosterone to exert either androgenic or indirect estrogenic actions, with the latter potentially increasing breast cancer risk. In experimental studies, androgens exhibit growth-inhibitory and apoptotic effects in some, but not all, breast cancer cell lines. Differing effects between cell lines appear to be due primarily to variations in concentrations of specific coregulatory proteins at the receptor level. In rodent breast cancer models, androgen action is antiproliferative and proapoptotic, and is mediated via the androgen receptor, despite the potential for testosterone and dehydroepiandrosterone to be aromatized to estrogen. The results from studies in rhesus monkeys suggest that testosterone may serve as a natural endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium. Epidemiological studies have significant methodological limitations and provide inconclusive results. The strongest data for exogenous testosterone therapy comes from primate studies. Based on such simulations, inclusion of testosterone in postmenopausal estrogen-progestin regimens has the potential to ameliorate the stimulating effects of combined estrogen-progestin on the breast. Research addressing this is warranted; however, the number of women that would be required for an adequately powered randomized controlled trial renders such a study unlikely.

Androgens↗
PubMed2004

The use of testosterone after menopause.

There is now substantial evidence from randomised controlled trials that testosterone therapy will improve sexual satisfaction and mood in surgically menopausal women treated with concurrent oestrogen, with less data in naturally menopausal women and premenopausal women. However, long-term safety data for combined-oestrogen testosterone therapy are lacking, and the effects of testosterone-only therapy in postmenopausal women are unknown. Although there appears to be considerable potential for testosterone to improve the quality of life for selected women, inappropriate and/or excessive use of testosterone carries the risk of masculinisation and possibly more serious side effects. All women treated with testosterone need to be carefully monitored both biochemically and clinically and should have long term follow up for adverse sequelae.

Aged↗