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We report a case of a female patient with chronic myelogenous leukemia who presented, 8 yr after initial diagnosis, with pancytopenia, encephalopathy, and myalgia. The tentative diagnosis was accelerated phase of chronic myelogenous leukemia. However, because the patient had been treated with cimetidine for 7 months we first omitted this drug. When cimetidine was stopped, bone marrow recovered, and myalgia and encephalopathy subsided. Immunological studies showed stimulation of the patient's lymphocyte blastogenesis by cimetidine and a marked increase in the proportion of cytotoxic/suppressor T lymphocytes after incubation of peripheral blood lymphocytes with cimetidine for 6 days. These findings indicate a role for cell-mediated immunity in the pathogenesis of cimetidine-induced pancytopenia in this patient. [ABSTRACT FROM AUTHOR]

Since the results of the women health initiative study showing an overall negative risk-benefit ratio with 0.625 mg of conjugated estrogens plus 2.5mg of medroxyprogesterone acetate, the use of the lowest effective dose of steroids in hormone replacement therapy (HRT) is recommended. A low-dose regimen appears to induce less side effects such as breast tenderness or leg pain than do higher dose preparations. The decrease in hot flashes with low-dose estrogens, range 60-70%, is less than the 80-90% reduction with standard dosing. But this mean that 60-70% of menopausal women do not need higher doses. The same applies to bone preservation which is dose dependent: the number of non-respondant women will be higher than with standard doses. However, randomized double-blind, placebo controls trials have defined positive effects on bone of low doses of HRT with adequate calcium and Vitamin D in elderly women. The use of bone densitometry and of biochemical markers of bone turnover is mandatory in women using low or ultra-low-dose preparations. In spite of the lack of trials conducted with low-dose HRT, this treatment seems to be safer: Beside the low-dose HRT, one must consider some other facts: In the future, it is conceivable that more comprehensive pharmacogenomic studies will lead to effective algorithms for individualizing the right dose of steroids to be used in HRT.

Menopause is a very important public health problem for many reasons. DEMOGRAPHIC: In 1990 there were 467 million women aged 50 years or more; worldwide, they will number 1200 million in 2030. SOCIOLOGICAL: The expectation of life in the Occident for a 50-year-old woman is a further 33 years, thus at this point, a menopausal women is still in active employment. PHYSIOLOGICAL: Menopause is not a disease, but gives rise to many problems which involve the entire body. MEDICAL: The only available treatment for this phase of the woman's life is oestrogens. These drugs induce many beneficial effects but the large-scale treatment of women who are not ill brings into question the harmlessness of this approach. ECONOMIC: The cost of medical treatment and regular review have to be considered in addition to the increased cost of pensions for these women. HUMAN: The improved quality of life observed with the medical treatment of such women could be an added dimension of the classical evaluation of the benefit/risk ratio.

Objectives: The objectives were to compare the local skin tolerability of a matrix-type estradiol transdermal system, Oesclim 50, with that of the reservoir-type system, Estraderm TTS 50., Methods: Two randomised studies were performed. In the first study, the modified Draize-Shelanski-Jordan method of sensitization was used in an open, parallel-group trial to compare the cutaneous tolerability of repeated applications of Oesclim 50 with that of Estraderm TTS 50 in 24 healthy postmenopausal women. The second study was an open, randomised, parallel-group, multi-centre clinical trial involving 283 healthy menopausal women. A total of 143 women were allocated to treatment with Oesclim 50 and 140 to Estraderm TTS 50. The treatment duration was four months., Results: The first study showed that the treatments, Oesclim 50 and Estraderm TTS 50, had no sensitizing potential and did not induce allergic reactions. In the second study, 4.2% of applications in the Oesclim group provoked reactions compared with 9.5% in the Estraderm group (P < 0.001). Thirty-seven patients (25.9%) treated with Oesclim and 55 patients (39.9%) receiving Estraderm experienced one or more reactions (P < 0.05). Redness and itching were the most frequent types of application site reaction in both treatment groups. The durations of the reactions were significantly shorter in the Oesclim group (P < 0.01), with a higher percentage of durations of less than 1 h and a lower percentage of durations of over 48 h than in the Estraderm TTS 50 group. None of the reactions in the Oesclim group led to premature removal of the patch, compared with 11 (3.4%) in the Estraderm group (P < 0.05). The number of patients who discontinued treatment due to application site reactions was one (0.7%) in the Oesclim group and seven (5.1%) in the Estraderm group (P < 0.05). Efficacy and general safety were comparable in the two treatment groups., Conclusions: In the first study, neither Oesclim nor Estraderm induced allergic reactions. In the second study, the local skin tolerability of Oesclim was significantly better than that of Estraderm, in terms of the number, duration and severity of the application site reactions.

Objectives: The objectives were to compare the tolerability, adhesion and efficacy of a new matrix-type estradiol transdermal system, Oesclim 50, with those of Estraderm TTS 50, a reservoir-type system., Methods: This was an open, randomised, parallel-group, multi-centre clinical trial, performed in six European countries. A total of 143 healthy menopausal women were allocated to treatment with Oesclim 50 and 140 to Estraderm TTS 50. The transdermal systems were applied twice weekly for 24 days out of each 28-day cycle, over a period of four cycles. Oral progestogen treatment was taken by non-hysterectomised patients for the last 12 days of estrogen therapy in each cycle., Results: The local skin tolerability of the Oesclim 50 transdermal system was significantly better than that of Estraderm TTS 50. In the Oesclim 50 group, 4.2% of applications caused a reaction, compared with 9.5% in the Estraderm TTS 50 group (P < 0.001). Safety assessments showed both treatments to be well tolerated. Seven patients in the Oesclim 50 group, and 12 in the Estraderm TTS 50 group, discontinued due to adverse events. Of these discontinuations, one (0.7% of patients) in the Oesclim 50 group and seven (5.1% of patients) in the Estraderm TTS 50 group were due to application site reactions (P < 0.05). There was no statistically significant difference between the two groups in the percentage of patients with signs of hyperestrogenism (29 patients (20.3%) in the Oesclim group and 28 patients (20.0%) in the Estraderm TTS 50 group). Adhesion was significantly better for the Oesclim 50 transdermal system, with 6.0% of Oesclim 50 applications becoming detached compared with 11.3% of Estraderm TTS 50 applications (P < 0.001). The greater adhesion of Oesclim 50 was particularly apparent when the systems were exposed to water, with three times fewer Oesclim 50 systems becoming detached during a shower or bath (P < 0.001 in each case). Both treatments produced significant and comparable improvements in vasomotor symptoms, other menopausal symptoms and gynaecological assessments. A near-maximal effect on vasomotor symptoms was observed after approximately 1 month of treatment, and was maintained for the entire treatment period., Conclusion: Overall, Oesclim 50 provided statistically significantly better local skin tolerability and adhesion than Estraderm TTS 50, together with comparable efficacy and safety.

We have carried out a general review of the problem of reversing the contraceptive mehtods using oestrogen-pregestogen contraceptives. We have very carefully reviewed the onset of long cycles showing clearly that they occur more easily in women who have started with irregular cycles, as do post-pill amenorrhoea cases. Spontaneous abortions seem to occur just as often after the pill as in the general population and the alarm that was raised by D. Carr seems to us to be very exaggerated. The infants are normal, have a lower perinatal mortality when we take into account the patients who use this method and there are no more congenital abnormalities than in other patients.

Hormonal therapy of the menopause can only be conceived with a careful choice of products and a judicious association of oestrogens and progestagens.