[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.]



Further articles in this publication


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


[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.]


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


[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.]


[István Krasznai, MD]



[Forthcoming congress]


[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.]

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Lege Artis Medicinae


KAHÁN Zsuzsanna

[Breast cancer is the most common malignancy in women in developed countries. The development of most breast cancers is related to various hormonal effects, while 10% is associated with inherited gene mutations. Most of the primary prevention methods aim at decreasing the effects of hormones, but education on proper lifestyle is also an important risk-lowering method. The primary treatment of early breast cancer is usually breast-conserving surgery, either with the targeted removal of regional lymph nodes (by sentinel lymph node labelling) or with axillary block-dissection. The aim of postoperative radiotherapy is the eradication of the tumour cells left behind. Beside the locoregional tumour control this also plays a role in the prevention of recurrence or a secondary systemic dissemination. Adjuvant systemic treatments are used for the eradication of disseminated microscopic tumour foci. The use of modern adjuvant treatments may reduce death from the disease by up to 50%. The risks of relapse or death may be estimated based on established prognostic factors. While in low-risk patients it is not worth starting medical treatment, especially in view of the side effects, while in other cases chemo- or hormonal therapy may save the patient's life. The choice of the medical treatment should also depend on the patient's general health, the concomittant diseases and her preferences. The collaboration of the various specialists involved in the care of breast cancer patients can best take place at specialised breast centres that are equipped with the necessary technical basis, knowledge and professional experience.]

Lege Artis Medicinae


MASSZI Gabriella

[The physiological changes of menopause are associated with an increase in cardiovascular risk. Cardiovascular diseases lead mortality statistics also in women. Several physiological effects of oestrogen are thought to be protective for the circulatory system. The reasonable idea of hormone replacement therapy, however, has not met the expectations. This article reviews the relevant studies and discusses the possible causes of failure. The second part focuses on the issue of prevention. The Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women, a recommendation developed in the US, is delineated. Hungarian data are provided based on results of the Menokard programme. The paper gives an overview of hormone replacement therapy and cardiovascular prevention in postmenopausal women.]

LAM Extra for General Practicioners

[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]


[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.]

Lege Artis Medicinae



[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.]