Faculty Bibliography

Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential role for TGF-beta s in the normal proliferative endometrium and its possible involvement in the transition to complex hyperplasia and progression to endometrial carcinoma. The angiogenic and mitogenic growth factor, basic fibroblast growth factor, was used for comparison. Differential TGF-beta isoform-specific immunoreactivity was observed in the normal endometrium, which is composed of glandular and stromal cells. There was an increase in TGF-beta 3 but not TGF-beta 1 or TGF-beta 2 in the glandular epithelium from the proliferative to the secretory phase of the menstrual cycle. Immunostaining for TGF-beta 2 was more intense in the stroma than the glands. In contrast, TGF-beta 1 and TGF-beta 3 were near equal intensity in these two endometrial compartments, TGF-beta 3 being the most intense. The glandular epithelium demonstrated a statistically significant stepwise increase in the expression of all three TGF-beta s progressing from the normal proliferative endometrium to simple hyperplasia and on to complex hyperplasia. However, the stromal cells maintained approximately the same level of immunoreactivity for TGF-beta in all these samples. In comparing proliferative endometrium with complex hyperplasia, there was a 5.1-, 3.4-, and 2.6-fold increase in immunostaining in the glands for TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively (P < or = 0.001). There was no further increase in immunoreactivity with progression from preneoplastic complex hyperplasia to carcinoma. Immunoreactive basic fibroblast growth factor was slight in normal endometrium and simple hyperplasia. There was a 4.6- and 4.2-fold increase in immunostaining observed in complex hyperplasia compared with proliferative endometrium in the glandular (P < or = 0.0054) and stromal (P < or = 0.0053) cells, respectively, with no further increase in carcinoma. By in situ hybridization, an increase in mRNA for all TGF-beta isoforms paralleled TGF-beta immunoreactivity. However, in contrast to the increased immunostaining in the glands in complex hyperplasia, there was remarkably more mRNA in the stromal cell compartment. The discordant expression of mRNA and protein was only observed in the pathological endometrium since both were more highly expressed in the stromal cells in normal proliferative endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

This was an open-label study comparing effects of a nonhormonal drug-free bioadhesive vaginal moisturizer to a local estrogen therapy in the treatment of vaginal dryness symptoms. There were 15 women evaluated in each treatment group during a 12-week period. Results indicated that the bioadhesive vaginal moisturizer was a safe and effective alternative to estrogen vaginal cream, with both therapies exhibiting statistically significant increases in vaginal moisture, vaginal fluid volume, and vaginal elasticity with a return of the premenopausal pH state

In the past, oral contraceptives contained much higher dosages of estrogen than those used in post-menopausal hormone replacement therapy. And it's true that the higher doses of estrogen can decrease the anti-clotting factors in the blood -- and contribute to the formation of clots. A few decades ago, when many women over 35 who were using these higher-dose oral contraceptives developed serious blood clots, researchers found that it was due to two things: higher doses of estrogen and aging. Since that discovery in the 1970s, the U.S. Food and Drug Administration has required that only low-dose oral contraceptives be prescribed to women over 35. After reducing the dosage of estrogen for this group of women, the incidence of blood clots decreased dramatically. It turns out that aging is as important a factor as dosage in regard to clotting

Although hormone replacement therapy (HRT) has been available for almost 100 years, conflicting opinions still exist about its efficacy and safety. There is uniform agreement that vasomotor instability and vaginal atrophy are totally reversible with HRT. Effective treatment of bone loss with HRT depends on the number of years of estrogen deprivation, peak bone mass, and rapidity of bone loss. Oral, transdermal, and pellet estrogens are equality effective. Mortality from coronary heart disease decreased 20% to 40% in women on HRT, yet the mechanism has not yet been ascertained. The increased risk of endometrial cancer has been confirmed, but better diagnostic techniques for detection in the precancerous state have been developed. The relationship of breast cancer to estrogen use has not been conclusive. Meta-analysis of 13 studies results in a relative risk of 1.06, whereas a large case-control study reveals a relative risk of 0.9. However, it is clear that in the average, healthy woman, low-dose estrogen replacement for less than 10 years does not increase the risk of breast cancer. Physicians are encouraged to help patients weigh the risks and benefits of HRT

OBJECTIVE: To review the incidence of breast cancer in a continuous 22-year study of conjugated estrogen-medroxyprogesterone acetate hormone replacement therapy. METHODS: Eighty-four pairs of continuously hospitalized postmenopausal women who were matched for age, smoking history, and medical diagnosis were treated with estrogen-progestin hormone replacement therapy or placebo in a prospective and double-blind manner for 10 years. In the subsequent 12 years, the women were offered the choice of starting, stopping, or continuing hormone replacement therapy. RESULTS: After the initial 10 years, the incidence of breast cancer in the placebo group was 4.8%, whereas no cancers were found in the hormone replacement therapy group (P = .12). After an additional 12 years of follow-up, the overall incidence of breast cancer in the women who had never taken hormone replacement therapy was 11.5%, whereas no breast cancers had developed in the women who had ever taken hormone replacement therapy (P < .01). CONCLUSIONS: These data suggest that the 22-year administration of estrogen-progestin hormone replacement therapy did not increase the incidence of breast cancer in a small group of continuously hospitalized postmenopausal women

Endometrial sampling is the mainstay of management of the postmenopausal patient with uterine bleeding. Thirty women with postmenopausal bleeding were studied prospectively. Before endometrial sampling, a vaginal probe ultrasonographic examination was performed. Eleven patients demonstrated a thin 'pencil line' endometrial echo in which the maximum anteroposterior thickness on the long axis view was less than or equal to 5 mm. All eleven patients had minimal tissue obtained on biopsy and a pathology report of 'tissue insufficient for diagnosis.' Seventeen patients had an echogenic endometrium greater than or equal to 6 mm. Pathology reports of their samples revealed tissue insufficient for diagnosis (two cases), proliferative endometrium (six), secretory endometrium (three), hyperplastic endometrium (three), polyp (two), and endometrial cancer (one case). Two additional patients had no endometrial echo visualized because of associated myomas. These findings suggest (1) that the absence of significant endometrial tissue (echo less than or equal to 5 mm) on vaginal ultrasonography in cases with postmenopausal bleeding is uniformly associated with tissue insufficient for diagnosis, and (2) when endometrial thickness is greater than or equal to 6 mm the histologic diagnosis should be determined in the pathology laboratory