OBJECTIVE

To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years.

DESIGN

This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial, a randomized, placebo-controlled, double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol. Four hundred seventeen postmenopausal women, aged 60 to 80 years, were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a standardized questionnaire.

RESULTS

At baseline, 16% of women reported hot flashes, 32% reported vaginal dryness, and 35% reported trouble sleeping. Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes, vaginal dryness, or sleep difficulties than those who received placebo. Treatment with ultralow-dose estradiol did not cause breast tenderness, uterine bleeding, or other symptoms often attributed to estrogen, but vaginal discharge was more common in women who received estradiol compared with those who received placebo.

CONCLUSION

In this population of older, largely asymptomatic women, ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge. Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger, more symptomatic women.

To exclude bacteria- or animal-derived factors from cultured fabrication of transplantable epithelial cell sheets, primary human oral mucosal epithelial cells were seeded on temperature-responsive culture inserts having submicron-scale pores. Supplying culture medium containing human autologous serum to both apical and basal sides of human epithelial cells allows these cells to grow to confluence. These proliferating cells created stratified epithelial layers even when 3T3 feeder layers and fetal bovine serum were eliminated from culture. Normal keratin expression profiles were obtained with these cells, and basal and midlayer cells expressed p63, a putative stem/progenitor marker. These results suggest that temperature-responsive culture inserts can be useful in clinical settings that require the exclusion of xenogeneic factors.

Cell-based therapies have now generated significant interest as novel drug delivery systems, with various adult cell types used in treating a wide range of diseases. To overcome the limits that restrict treatments for corneal surface dysfunction, corneal epithelial stem cells expanded ex vivo have been applied as an alternative approach. While previous studies used various carrier substrates, we present a novel method using cell sheet engineering with temperature-responsive culture dishes to create carrier-free corneal epithelial stem cell sheets that can be transplanted without sutures. Results from clinical trials reveal successful transplantation with the recovery of lost visual acuity in all cases. Cell sheet engineering, therefore, presents a novel method for the delivery of corneal epithelial stem cells, and can also be applied for other approaches of cellular therapeutics.

BACKGROUND

With recent advances in breast cancer risk reduction practices, it is increasingly important to assess both the breadth of and disparities in use across different racial/ethnic groups.

METHODS

We conducted telephone interviews with 1,700 women ages 40 to 74, from four racial/ethnic groups, without prior history of breast cancer, who received mammograms at one of five mammography facilities in San Francisco. Main outcomes measured included recognition of tamoxifen, raloxifene, genetic testing, and prophylactic surgery. Global indicators (recognition of any therapy, discussion of breast cancer risk) were developed from original outcome measures and analyzed using logistic regression.

RESULTS

Multivariate analyses indicate that race/ethnicity and interview language affected recognition of therapies and discussion of risk. White women were more likely than all other women to recognize any therapy and more likely than Asian-Americans to discuss risk. Women at high risk, who had a prior abnormal mammogram, who perceived themselves to be at high risk, or who were exposed to breast health information were more likely to discuss risk.

CONCLUSIONS

Women are aware of preventive therapies, although discussion and use is limited. Interventions to increase use of therapies should focus on those at high risk.

Current guidelines recommend that postmenopausal hormone therapy (HT) be used primarily for treatment of vasomotor and urogenital symptoms associated with the menopausal transition and that women use the lowest effective dose for the shortest time necessary. Vasomotor symptoms improve or resolve spontaneously within a few months to a few years of onset in the majority of women, suggesting that most women should be able to discontinue HT within a few years of starting treatment. Approximately 75% of women who try to stop are able to stop HT without major difficulty. However, some women who would like to stop HT are unable to do so, mainly owing to the development of vasomotor symptoms. Troublesome symptoms associated with stopping HT appear to be more common among women who start HT for treatment of symptoms, but they also are reported by women who started HT for other reasons, such as prevention of osteoporosis. Unfortunately, little information is available to guide physicians in helping women who have difficulty stopping HT. Many clinicians recommend slowly tapering HT or adding another drug for treatment of hot flashes, but the effectiveness of these approaches has not been evaluated. For women who cannot tolerate even a slow taper, the value of symptom relief likely outweighs any increased risks due to HT use.