Ca&Bone

[The role and effects of progestogens in menopausal hormone therapy]

ÁCS Nándor, MERICLI Metin, VERMES Gábor, LANGMÁR Zoltán

MAY 20, 2004

Ca&Bone - 2004;7(02)

[The adequate therapy of postmenopausal hormone deficiency is estrogen replacement. However, the risk of endometrium hyperplasia and carcinoma is significantly increased among users of estrogen as monotherapy.To minimize the risk of endometrial cancer, a progestogen must be added to estrogen therapy. While progestogens may inhibit the cardiovascular effects of estrogens, they do not significantly influence the effects of estrogen on bone. The increased risk of breast cancer among menopausal hormone therapy users seems to be the consequence of progestin administration.There are notable differences among progestins in their effects and side effects, thus, in the future, therapeutic protocols should be tailored individually.The differential effects of various progestogens is an exciting area to study, partly because it may have clinical consequences, partly, because it provides opportunities for far-reaching research.]

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Ca&Bone

[The role of alfacalcidol in the prevention of osteopenia following renal transplantation]

BERCZI Csaba, ASZTALOS László, KINCSES Zsolt, BALOGH Ádám, LŐCSEY Lajos, BALÁZS György, LUKÁCS Géza

[AIM - The aim of this prospective study was the long-term evaluation of the effect of calcium and alfacalcidol treatment on calcium metabolism in patients with renal transplantation. METHODS - Patients were divided in two groups. Patients in Group 1 (n=159) received calcium substitution, while patients in Group 2 (n=81) were treated with alfacalcidol. Serum Ca, P, Mg, alkaline phosphatase (AP) and PTH levels were determined before and after transplantation regularly for three years. Femur neck and lumbar vertebral bone mineral densities (BMD) were measured at the same time after transplantation. RESULTS - After transplantation the mean serum calcium level significantly increased, while the mean serum phosphate level significantly decreased in both groups. After the operation the PTH levels decreased in both groups and it was found to be more pronounced in the alfacalcidol group.The majority of patients had osteopenia in the follow-up period. Between the third month and the third year after transplantation, BMD increased by 9.4% in Group1, and decreased by 4% in Group 2 at the lumbar spine. At 3 years the mean BMD value at the femoral neck was increased by 6.5% in Group 1, and by 6.7% in Group 2, compared to the 3-month values.The change in BMD was only significant at the lumbar spine, in Group 1 (p=0.019). During the follow-up period osteonecrosis was diagnosed in 6 patients in Group 1 and in 9 cases in Group 2. CONCLUSION - Alfacalcidol treatment decreased secondary hyperparathyroidism more rapidly and effectively, which was also indicated by the more pronounced decrease of serum PTH levels. During the 3 years follow-up period, BMD increased in both groups except for the lumbar spine in Group 2, however, the majority of the patients still had osteopenia.The study could not demonstrate a superiority of alfacalcidol over calcium supplementation in the prevention of posttransplantational osteopenia.]

Ca&Bone

[István Krasznai, MD]

FÖLDES János

Ca&Bone

[Bone metabolism and body mass index in postmenopausal women]

TÁRCZY Csaba,Toldy Erzsébet, SZERB János, VARGA László

[INTRODUCTION - In addition to several other causes constitutional factors play an important role in the development of osteoporosis.Various aspects of bone metabolism were examined to explain the differences in bone density between women with low and high body mass index (BMI). PATIENTS AND METHOD - One hundred and ninetytwo postmenopausal women were included in the study. Bone density was measured by forearm densitometry.To assess bone formation, serum osteocalcin levels were measured, while the rate of bone absorption was estimated from C-terminal telopeptide levels of collagen type I measured in urine and blood. RESULTS - The prevalence of osteoporosis was higher in women with low BMI than in those with normal or higher BMI. Bone metabolism - both formation and absorption - was increased in both groups, however, in women with low BMI this increase was more pronounced and bone metabolism tended to be shifted to absorption compared to patients with normal or higher BMI. CONCLUSION - Postmenopausal lean women have accelerated bone metabolism compared to obese women. This fact and the shift to absorption may be the main reasons for the higher frequency of osteoporosis found by densitometry in women with low BMI than in those with higher BMI.]

Ca&Bone

[Evaluation of quality of life following treatment with calcitonin nasal spray in patients with osteoporosis: preliminary results of the MERLIN study]

BORS Katalin, KÓSA József, BORBÉLY Judit, TABÁK Ádám, HORVÁTH CSABA

[INTRODUCTION - MERLIN (Management of Osteoporosis in Elderly with Calcitonin) is an open-label, multicenter, prospective, follow-up study conducted in Hungary, part of which is to assess the impact of treatment with Miacalcic, - an intranasal salmon calcitonin, on the quality of life (QoL) among patients with osteoporosis. In this paper we report the preliminary results of the MERLIN study. PATIENTS - The study initially involved 1949 senior patients (aged >65 years) to whom calcitonin was prescribed for osteoporosis according to the application instructions. Patients presented at outpatient clinics and consisted of two groups; they were either newly diagnosed or they had been receiving a therapy for osteoporosis other than calcitonin. METHODS - This latter group discontinued their previous treatment and all patients received 200 IU intranasal salmon calcitonin (SCT) once daily for three months. Patient and physician questionnaires were used to collect information on the patients' QoL (EQ-5D VAS) and their general well-being at baseline and at follow-up visits at week 4 and week 12. RESULTS - Calcitonin use was associated with improvements in all EQ-5D domains and component scores as well as in VAS. Patients with previously known osteoporosis who, switched to calcitonin therapy achieved better results (0,046 QALY), than the newly diagnosed patients (0,0405 QALY). CONCLUSIONS - We conclude that intranasal SCT 200 IU daily is safe and effective in improving QoL of both, male and female patients with low bone mineral density.The conclusions that can be drawn from this study are limited due to the lack of a control group and to the unblinded design. Further placebo-controlled studies are needed to confirm these results. Nevertheless, our study was the first in Hungary to evaluate the quality of life impact of an osteoporosis treatment, and hopefully it will be followed by more such studies directed to other osteoporosis treatments.]

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[Postmenopausal changes of immune system-related genes expression in human bone tissue]

BALLA Bernadett, KÓSA P. János, KISS János, PODANI János, TAKÁCS István, LAZÁRY Áron, BÁCSI Krisztián, NAGY Zoltán Zsolt, SPEER Gábor, LAKATOS Péter

[INTRODUCTION - The molecular and cellular interactions between the immune system and bone tissue have been established. Sex hormone deficiency at the time of menopause has multifunctional role by influencing growth, differentiation and metabolism of the skeletal and the immune system. We have used non-parametric and multidimensional expression pattern analyses to determine significantly changed mRNA profile of immune system-associated genes in postmenopausal (POST) and premenopausal (PRE) non-osteoporotic bone. MATERIALS AND METHODS - Ten bone tissue samples from POST patients and six bone tissue samples from PRE women were examined in our study. The transcription differences of selected 50 genes were analyzed in Taqman probe-based quantitative real-time RT-PCR system. RESULTS - Mann-Whitney test indicated significantly down-regulated transcription activity of 3 genes (CD14, HLA-A, ITGAM/CD11b) and upregulated gene expression of 6 genes (C3, CD86, IL-10, IL-6, TGFB3, TNFSF11/RANKL) in POST bone. According to the canonical variates analysis results, the groups of postmenopausal and premenopausal women are separable by genes coding for cytokines, co-stimulators and cell surface receptors affected in antigen presentation and T cell stimulation which have high discriminatory power. CONCLUSIONS - Based on a complex gene expression patterns in human bone cells, we could distinguish POST and PRE states from an immunological aspect. Our data might provide further insight into the changes of the intersystem crosstalk between immune and skeletal system, as well as local immune response in the altered microenvironment of POST bone.]

Lege Artis Medicinae

[POSTMENOPAUSAL HYPERTENSION]

SZÉKÁCS Béla

[Women with normal cycles on the average have lower blood pressure than age matched men. From the fifth decade of life increasing average blood pressure values of females reach or even exceed the levels of males. The frequency of hypertension among women in menopause and postmenopause is 3-4 times greater than in premenopause. This great difference can not be explained by the age dependent increase in blood pressure. There are several pathological components in the background of the elevation of blood pressure following the reduction and failure of female sex hormone production. Among these components are lifestyle changes, reduced physical activity, growing body weight, increased sympathetic activity, higher RAS (renin-angiotensin system) influence and increased salt dependence of blood pressure seem to be the dominant factors. Contrary to earlier suggestions recent clinical findings have proved that estrogen or combined hormone replacement therapy did not increase but rather slightly reduced the blood pressure in menopausal and postmenopausal hypertensive women. Therefore, hypertension itself should not be the contraindication against carefully managed hormone replacement therapy. The therapy is frequently used for preventing severe osteoporosis in spite of the disappointing cardiovascular results of the WHI and HERS trials. In the Joint National Committee 7 there are no special recommendations which would strictly prefer one or another antihypertensive agents in the pharmacological treatment of postmenopausal hypertension. However doctors are assisted in their individual therapeutical decisions by certain clinical and experimental findings which refer to higher sympathic activity, enhanced RAS influence and increased salt dependency in the pathomechanism of postmenopausal hypertension.]

Hypertension and nephrology

[Hypertension and menopause]

MASSZI Gabriella

Lege Artis Medicinae

[Special problems of hypertension in women]

KAPOCSI Judit, DEÁK György

[Menopause and pregnancy are especially vulnerable periods of women’s life regarding hypertension. The “Guidelines for the Management of Arterial Hypertension”, issued by the European Society of Hypertension and the European Society of Cardiology, dedicates a separate chapter to hypertension in women. The renewed guidelines of the Hungarian Society of Hypertension also pays a special attention to hypertension detected during pregnancy. In this article, the euthors review the topics of hypertension detected during menopause and pregnancy, discussing pathomechanism and therapy.]

Lege Artis Medicinae

[Changes in the hormonal therapy of breast cancer patients]

MOSKOVITS Katalin

[The hormonal therapy for breast cancer patients seems to be changing. At present the new, third generation aromatase inhibitors are the standard second line therapy for postmenopausal, receptor positive advanced breast cancer patients. Currently, tamoxifen (TAM) stands as the ”gold standard” first line therapy, with ist role changing, due to the aromatase inhibitors which seems to be more effective than TAM and have less side-effects. For these reasons, aromatase inhibitors may be useful in the adjuvant setting, but long-term side-effects are not yet known. In the next few years, sufficient experience will be gained with these drugs which might help us to change practice. Pure antioestrogens are also promising new drugs. Recently, the LHRH analogues were the preferred drug of choice in premenopausal women, in contrast to surgical or radiological ovarian ablation. All receptor positive breast cancer patients should receive hormonal therapy, regardless of age, menopausal status, node status, tumour size, but we should avoid hormonal therapy for the endocrine nonresponsive patients.]