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Susan R Davis

Publications and source records attributed to Susan R Davis.

At least 37 records · Page 2Linked to original sources
PubMed2003

Menopause: new therapies.

The risk-benefit ratio of traditional postmenopausal hormone therapy is considered by many to be unacceptable. Low-dose oestrogen-progestin therapy (oral or non-oral and continuous or pulsatile) may have a better risk-benefit ratio, but this remains unproven. Steroids with selective tissue activation, such as tibolone, alleviate symptoms and protect against bone loss, but long-term safety data are lacking. Selective oestrogen receptor modulators (SERMs), such as raloxifene, prevent bone loss when used alone, and may soon be combined with oestradiol to treat symptoms and prevent osteoporotic fracture. Effects of SERMs on the cardiovascular system are currently being evaluated.

Administration, Cutaneous↗
PubMed2003

Androgens in women.

The role of androgen treatment in women remains controversial. The proposed "Female Androgen Insufficiency Syndrome" (Fertility and Sterility, April 2002) describes a number of non-specific symptoms including unexplained fatigue, decreased well being/dysphoric mood and/or blunted motivation and diminished sexual function. An estimated 40% of women experience sexual dysfunction, highlighting the need for ongoing research into this field in order to fully define the possible contribution of androgen insufficiency. The increasing availability of products, such as dehydroepiandrosterone (DHEA) supplements also points to the need for controlled studies to assess the safety of these and other preparations. Measurement of androgens in women requires sensitive assays with the ability to detect low levels and a narrow range with precision. Normal ranges of androgens for women of reproductive and post-reproductive age remain poorly defined. Debate exists as per importance of measurement of free versus total testosterone, with the "free androgen index" offering an alternative method of assessment of testosterone availability. Testosterone treatment is being developed for women in the form of transdermal patches, gels or cream, with percutaneous implants in common usage in some countries. Recent research has highlighted alternative means of administration, such as oral inhalation or buccal lozenge. DHEA is widely available in some countries. Research to date has demonstrated improvements in libido and sexual function, mood and well being. Evidence points to other potential benefits of androgen treatment, including preservation of bone mass, a possible protective role in breast cancer and beneficial effects on cognition. Adverse effects of androgen treatment in women are dose-dependent and include virilisation, mood disturbance and acne. These are uncommon if appropriate doses are administered and highlight the need for treatment to be closely monitored clinically and biochemically. Beneficial effects of testosterone treatment in post-menopausal women with lowered androgen levels have been well documented, and preliminary evidence suggests a role for treatment in pre-menopausal women with symptoms and lowered testosterone levels.

Aging↗
PubMed2003

The role of androgen therapy.

The concept of a female androgen insufficiency syndrome, although not new, remains somewhat controversial. Androgens are quantitatively the predominant sex steroid in women, circulating in the micromolar and nanomolar concentration range, compared with picomolar levels of oestrogens. The most significant biologically active androgen is testosterone (T), which circulates bound tightly to sex-hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG-bound fraction is the bioavailable moiety. Hence, clinically useful T measurements require data on total concentrations as well as SHBG level. Testosterone insufficiency occurs in a number of circumstances, including hypopituitarism, premature ovarian failure, adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (causing elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen insufficiency include loss of libido, diminished well-being, fatigue and blunted motivation and have been reported to respond well to T replacement, generally without significant side-effects.

Androgens↗
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↗
PubMed2003

What is the rationale for androgen therapy for women?

To date, no formal definition of female androgen insufficiency (FAI) based on strong epidemiological data exists. However the proposed key symptoms of FAI, being reduced libido, diminished well-being, and lowered mood, have been reported to respond well to testosterone replacement, generally without significant adverse effects. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of estrogens. Androgens have important physiological roles in women, acting both as precursors for estrogen biosynthesis and directly via the androgen receptor. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone binding globulin and loosely to albumin. Circulating androgen levels decline in the years preceding menopause. This may be attributed to the gradual reduction in adrenal androgen production with age and to the loss of cyclical ovarian androgen production in the late reproductive years. Those who experience surgical menopause, have adrenal insufficiency or pituitary insufficiency, or those who experience premature ovarian failure, also have reduced androgen production. Androgen replacement therapy in the form of either dehydroepiandrosterone or testosterone is becoming increasingly widespread for the treatment of FAI. Evidence exists for the benefits of such therapy in relieving both the physical and psychological symptoms thought to be due to FAI in clinically affected women. However, clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety remain lacking.

Affect↗
PubMed2002

Testosterone insufficiency in women: fact or fiction?

Androgen deficiency in women is a valid diagnosis in premenopausal, as well as in postmenopausal women, under certain conditions. This diagnosis is hampered by a lack of precise definitions and sensitive assays for testosterone. Precise normal ranges for control populations are lacking, and thus many studies have used pharmacological instead of physiological levels of testosterone in treatment protocols. Despite these shortcomings, and a shortage of controlled studies, there is ample evidence that testosterone treatment has helped many women with signs and symptoms of deficiency.

Aging↗
PubMed2002

When to suspect androgen deficiency other than at menopause.

OBJECTIVE: To review causes of female androgen insufficiency (FAI) other than menopause. DESIGN: A review of the available literature in this field. RESULT(S): Androgen levels decline with increasing age during the reproductive years in healthy women and vary little or not at all across menopause, with controversy as to whether levels change in the postmenopausal years. Thus the premenopausal decline in androgens potentially is the most common cause of female androgen insufficiency (FAI), whereas natural menopause in itself is not a cause of androgen deficiency. Pathophysiological causes of FAI can be divided into those that affect ovarian androgen production, those that affect adrenal androgen production, and combined deficiency states. Surgical menopause is characterized by an abrupt onset of symptoms, in contrast to a more insidious onset of relatively nonspecific symptoms in women who have FAI due to aging. CONCLUSION(S): The decline in testosterone with normal aging before menopause may well be the most common cause of FAI, although many women do not present with symptoms and most are not diagnosed until they have reached menopause.

Adrenal Glands↗
PubMed2002

The role of androgen therapy.

The concept of an androgen deficiency syndrome in women is a relatively old one, although it has gained substantially increased attention in recent years. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of oestrogen. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG bound fraction is the bioavailable moiety. Hence interpretable testosterone measurements require data on total concentrations as well as the SHBG level. Testosterone deficiency occurs in a number of situations such as hypopituitarism, primary ovarian and adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (due to the elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen deficiency include lethargy, tiredness and loss of sex drive and interest, and have responded well to androgen replacement, generally without significant side-effects.

Adult↗
PubMed2002

Estrogen regulates development of the somatic cell phenotype in the eutherian ovary.

Steroids play a critical role in gonadal differentiation in birds, reptiles, and amphibia whereas gonadal differentiation in mammals is thought to be determined by genetic mechanisms. The gonads of female mice incapable of synthesizing estrogens due to disruption of the aromatase gene (ArKO) provide a unique model to test the role of estrogen in regulating the gonadal phenotype. We have shown that in the absence of estrogen, genetically female mice develop testicular tissue within their ovaries. The ovaries develop cells that possess structural and functional characteristics of testicular interstitial cells and of seminiferous tubule-like structures lined with Sertoli cells. Moreover, the ovaries express mRNA for the testis-specific Sertoli cell transcription factor Sox 9 and espin protein, which is specific for inter-Sertoli cell junctions. The development of the testicular tissue in this model can be reverted/postponed by replacing estrogen. When ArKO female mice were fed a diet containing phytoestrogens, the appearance of Leydig and Sertoli cells was postponed and reduced. Furthermore, administration of estradiol-17beta decreased the number of Sertoli and Leydig cells in the ovaries. These findings constitute definitive evidence that estrogen plays a critical role in maintaining female somatic interstitial and granulosa cells in the eutherian ovary.

Animals↗
PubMed2002

Compartment differences in knee cartilage volume in healthy adults.

OBJECTIVE: It is unclear why there are compartmental differences in the risk of knee osteoarthritis (OA). We investigated whether there are compartment differences in the volume of knee cartilage in healthy persons and identified determinants of medial and lateral tibial cartilage volume. METHODS: A total of 166 healthy persons (age range 21-79 yrs, 58% female) with clinically and structurally normal knees were examined. Thickness and volume were determined for the medial and lateral tibial articular cartilages by processing images acquired in the sagittal plane using T1 weighted fat saturated magnetic resonance imaging on an independent work station. RESULTS: In every subject, the lateral tibial cartilage was thicker than medial cartilage (mean 6.43 +/- SD 1.25 mm vs 4.49 +/- 0.81 mm; p < 0.001), and the volume of cartilage was greater (2.34 +/- 0.70 ml vs 1.82 +/- 0.56 ml; p < 0.001). This effect persisted when values for men and women were analyzed separately. Both medial and lateral tibial cartilage volume and thickness were greater in men compared to women, independent of body mass index and bone size. The reduction in medial and lateral tibial cartilage volume and thickness was inversely related to the current level of physical activity. CONCLUSION: This study supports the knee compartment differences in cartilage volume recently reported in children. It is likely these differences are maintained throughout life. The possibility that the amount of knee cartilage in an individual is a risk factor for OA now needs to be tested in longitudinal studies.

Adult↗
PubMedDate not supplied

Treatment of menopausal symptoms: what shall we do now?

During the past few years, many women and doctors have revised their opinions of hormone replacement therapy (HRT) for menopausal symptoms, and a substantial number of individuals have discontinued its use because of concerns about side-effects. Numerous alternatives to HRT are promoted, and assessment of the quality of evidence about the safety and effectiveness of these compounds can be difficult. In this Review, we summarise the data from studies addressing the efficacy, risks, and benefits of frequently prescribed treatments, and offer evidence-based clinical guidelines for the management of menopausal symptoms. Although few comparative studies exist, oestrogen alone or combinations of oestrogen and progestagen are likely to be the most effective treatments for menopausal hot flushes and vaginal dryness. Tibolone is as effective as HRT, however, and might also improve libido. For those who wish to avoid hormonal treatments, there are few effective options. Selective serotonin reuptake inhibitors might be effective in the very short term (less than 12 weeks) and are well tolerated. There is not enough evidence that any of the complementary therapies available are any better than placebo for menopausal vasomotor symptoms, and few safety data exist.

Breast Neoplasms↗
PubMedDate not supplied

The effects of tibolone on mood and libido.

OBJECTIVE: To review published data pertaining to the effects of tibolone on sexual parameters, mood, and cognitive function in postmenopausal women. DESIGN: A review of all relevant published, peer-reviewed studies. RESULTS: Tibolone is a compound that can be selectively metabolized by individual tissues to its estrogenic, progestogenic, or androgenic metabolites and hence exhibits tissue-specific hormonal effects. Tibolone also lowers sex hormone binding globulin, thus increasing free estradiol and testosterone levels. Tibolone alleviates climacteric vasomotor symptoms and displays a dominant progestogenic effect on the endometrium. Tibolone normalizes the vaginal karyopyknotic and maturation indexes and alleviates symptomatic atrophic vaginitis. Women treated with tibolone report significant reductions in vaginal dryness and dyspareunia, effects that may be secondary to both estrogenic and androgenic actions. Randomized studies indicate tibolone has positive effects on mood compared with placebo and alleviates several adverse mood parameters to a similar extent as conventional hormone replacement therapy. Improved mood is associated with increased plasma beta-endorphin. With respect to cognition, tibolone seems to improve semantic memory but does not significantly improve recognition memory. Tibolone is associated with improvements in sexual function that seem to be greater than those achieved with standard hormone replacement therapy. CONCLUSION: Published studies indicate beneficial effects of tibolone on both libido and mood, which otherwise significantly compromise physical, psychological, and social well-being. Hence, tibolone provides another option for menopausal women experiencing loss of libido as part of their symptomatology or who have persistent low libido despite adequate estrogen/progestin replacement therapy.

Affect↗
PubMedDate not supplied

Climacteric symptoms among indigenous Australian women and a model for the use of culturally relevant art in health promotion.

OBJECTIVE: To evaluate climacteric symptoms among rural and remote, indigenous Australian women and to develop culturally relevant women's health midlife educational material. DESIGN: A cross-sectional pilot survey based on structured interviews of women older than 18 years of age who were available for interview and willing to participate. The study was conducted in the Kimberley region of Western Australia and southwestern Victoria between February and June 1999. Health issues central to the local community were identified by the structured survey. Development of culturally relevant information involved collaboration between indigenous women and indigenous artists, health workers, educators, and ourselves. Traditional health themes in art form were then linked with specific health issues to be addressed. Health messages were translated by Aboriginal women and health workers into both traditional language and vernacular, to target all women. RESULTS: Fifty-five women completed the survey. Thirty-eight were premenopausal, 4 were perimenopausal, and 13 were postmenopausal. The 4 perimenopausal women and 9 of the 13 postmenopausal women had climacteric symptoms, but none had been prescribed systemic or local hormonal therapy. Rates of obesity, diabetes mellitus, and hypertension were high. Midlife women's health booklets were produced in collaboration with Aboriginal elders and artists to communicate preventive health information in a visual context familiar to Aboriginal people of the Kimberley and surrounding communities. CONCLUSIONS: In contrast to the case in other non-Caucasian populations, climacteric symptoms seem to be common among Australian indigenous women and are apparently untreated. Aboriginal art and language has been employed in the development of culturally appropriate health promotion literature for Aboriginal communities in the Kimberley region of Western Australia. This process of collaboration provides a useful model for addressing women's health issues in other culturally diverse populations.

Adult↗
PubMedDate not supplied

Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women.

OBJECTIVE: Circulating testosterone in women declines during the late reproductive years such that otherwise healthy women in their 40s have approximately half the testosterone level as women in their 20s. Despite this, research showing the benefits of androgen replacement has been limited to the postmenopausal years. In view of the known premenopausal physiological decline in testosterone, we have evaluated the efficacy of transdermal testosterone therapy on mood, well-being, and sexual function in eugonadal, premenopausal women presenting with low libido. DESIGN: Premenopausal women with low libido participated in a randomized, placebo-controlled, crossover, efficacy study of testosterone cream (10 mg/day) with two double-blind, 12-week, treatment periods separated by a single-blind, 4-week, washout period. RESULTS: Thirty-four women completed the study per protocol, with 31 women (mean age 39.7 +/- 4.2 years; serum testosterone 1.07 + 0.50 nmol/L) providing complete data. Testosterone therapy resulted in statistically significant improvements in the composite scores of the Psychological General Well-Being Index [+12.9 (95% CI, +4.6 to +21.2), P = 0.003] and the Sabbatsberg Sexual Self-Rating Scale [+15.7 (95% CI, +6.5 to +25.0), P = 0.001] compared with placebo. A mean decrease in the Beck Depression Inventory score approached significance [-2.8 (95% CI, -5.7 to +0.1), P = 0.06]. Mean total testosterone levels during treatment were at the high end of the normal range, and estradiol was unchanged. No adverse effects were reported. CONCLUSIONS: Testosterone therapy improves well-being, mood, and sexual function in premenopausal women with low libido and low testosterone. As a substantial number of women experience diminished sexual interest and well-being during their late reproductive years, further research is warranted to evaluate the benefits and safety of longer-term intervention.

Administration, Cutaneous↗