EMAS 2003 Bucharest 24 – 28 May 2003

Pulsed estradiol and breast cancer cell proliferation
New findings show that short-term application of estradiol is able to stimulate breast cell proliferation to the same degree as continuously administered estradiol in high concentrations. The researchers suggest that it is therefore "questionable" whether such "pulsed" estradiol therapy may reduce the breast cancer risk during HRT.

Serum concentrations after nasal estradiol application are up to 15- to 30-fold higher compared with oral or transdermal HRT. Since this is only a short-time peak, it has led to speculation that the breast cancer risk compared with conventional HRT may be reduced because of lower activation of the estradiol-receptor-transcription cascade.

However, Dr. Alfred Mueck at the University Women's Hospital, in Tübingen, Germany, presented details of a study testing estradiol at levels corresponding to the serum levels achieved with nasal application using the MCF-7 breast cancer cell line.

The results showed that estradiol in concentrations achieved with "pulsed" HRT was able to elicit proliferation of MCF-7 cells after an incubation time of 10 minutes. This correlates with the minimum exposure time using nasal estradiol application. Moreover, no significant differences were observed with non-stop continuous estradiol added in the same high concentration during 4 days.

Concluding, Mueck commented: "We were surprised by the findings, but they indicate that it is very unlikely that breast cancer risk is reduced with pulsed estrogen therapy. Clinical studies are urgently needed to reveal the breast cancer risk during nasal estradiol application, especially since this risk might be increased dependent on the achieved concentrations."

Further evaluation of cardiovascular effects required
The cardiovascular effects of HRT may depend critically on dosage and type of hormones, according to Dr. John Stevenson of Imperial College London, UK. He told delegates that despite findings from recent trials, the cardiovascular effects associated with treatment were far from established and warranted further evaluation.

Stevenson suggested that the cardiovascular harm identified in the HERS and WHI trials—both of which used conjugated equine estrogens (CEE) 0.625 mg, and medroxyprogesterone acetate (MPA) 2.5 mg—may relate to the dose of estrogen being too high or an adverse progestogen effect. He said: "In contrast, WHISP, an acute secondary prevention pilot study using low dose estradiol 1 mg and norethisterone acetate 0.5 mg, did not find an early increase in CHD events and tended to a reduction."

As a result, Stevenson said there remained a need to assess lower doses, different regimens, and alternatives to HRT including tibolone and SERMs [selective estrogen receptor modulators], adding: "It is still possible that HRT or alternatives may yet prove to have a major role in ensuring female health."

Dr. Gregory Evans (Wake Forest University School of Medicine, Winston-Salem, USA) presented results from OPAL, one of the first large randomized studies to evaluate the effects of menopausal therapies on carotid atherosclerosis in healthy postmenopausal women. The study recruited 866 healthy postmenopausal women who were randomly assigned to either 2.5 mg tibolone, 0.625 mg CEE plus 2.5 mg MPA, or placebo. Preliminary results showed that treatment over 3 years appeared to be associated with a very small but significant increase in carotid artery thickness in both active treatment groups.

Sexual problems in older women warrant more attention
Women who experience reduced sexual well-being following the menopause deserve greater medical care and attention, said Dr. Alessandra Graziottin (Center of Gynaecology and Medical Sexology, Milan, Italy) who spoke out against the continuing taboo that surrounds sexuality in older women.

"Sex is considered increasingly inappropriate after the menopause, still a taboo for many patients and physicians. It would seem that sexuality in women over 50 violates the principle of sexuality as a behavior appropriate for the young and fertile," she told delegates, adding that the caring and unbiased physician may greatly contribute to the quality of life and sexual life of women through an appropriate medical and psychosexual approach.

In the same symposium, Professor Rik van Lunsen (Department of Sexology, University of Amsterdam, and The Netherlands) presented evidence showing that tibolone has positive effects on arousability, frequency of sexual thoughts/fantasies and frequency of sexual desire. He also presented results suggesting that it restores vaginal blood flow in postmenopausal women to levels comparable to premenopausal women.

Safety of testosterone patches in surgically menopausal women
New findings from two trials indicate that "no clinically serious safety concerns" are detected in patients treated with transdermal testosterone doses of up to 450 mcg per day, according to trial investigator Dr. James Simon (George Washington University School of Medicine, USA).

However the claim prompted WHI investigator Dr. Jacques Rossouw (National Heart, Lung and Blood Institute, in Bethesda, USA) to caution that it was impossible to talk about the safety of testosterone until "we know more about its cardiovascular safety." He suggested that the USA's Food and Drug Administration would also be interested in this.

Simon presented the results from two double-blind, multicenter 6-month trials. They were set up to evaluate the safety and tolerability of transdermal testosterone patches in surgically menopausal women with hypoactive sexual desire disorder receiving estrogen therapy.

In one trial, 447 women receiving oral estrogen therapy were randomized to receive placebo or testosterone treatment in daily dosages of between 150 and 450 mcg. A 6-month extension included 155 women. In the second trial, 77 women on transdermal estrogen therapy received placebo or 300 mcg testosterone daily.

Simon reported that safety assessments including liver function, hematology, carbohydrate metabolism, lipid profiles, clotting parameters, acne and hirsutism were essentially unchanged from baseline at 6 months, in both studies. He added: "Adverse events remained low in frequency and comparable among the four treatment groups except for an increase in hirsutism in the 450 mcg per day group. All hirsutism adverse events were assessed as mild or moderate." The patch also showed good skin tolerability. Simon added that the efficacy results would be presented later in the year.

Call to restore public and professional respect
Explaining his comments, he said: "The success of HRT was stopped 5 years ago by the HERS study and then was recently shattered by the WHI study and by the listing of estrogens as carcinogens in the USA. Nowadays the professional and lay press point their fingers at the gynecologists presenting them as the enemy of the people."

Consequently, Toth urged delegates to work together to restore public respect for the profession. Elaborating, he said: "We need to recommend healthy lifestyle, diet and exercise, and screen patients more rigorously with the help of a multidisciplinary team. We need to discuss indications, contraindications and side effects in more detail before we offer hormonal therapy, and ensure that we treat or continue to treat symptomatic women checking them regularly and reconsidering the need for therapy on an annual basis.

"We should also individualize the hormonal preparation and form of application and we should not forget about the alternative options such as SERMs [selective estrogen receptor modulators], tibolone and [phytopharmaceuticals]."

Top ^

Powered by

  Copyright © 2005 www.waithong.com All right Reserved.
Email : Contact@waithong.com