Lars-Åke Mattsson

Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: A double-blind placebo-controlled study

OBJECTIVEnThe effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a randomized trial over 12 weeks.nnnSTUDY DESIGNnTwo hundred forty-two women were randomized, and 223 were analyzed for efficacy (n = 112 for estradiol and n = 111 for placebo). The quality of life was assessed by means of a battery of standard questionnaires.nnnRESULTSnQuality of life improved after both therapies, but health-related quality of life (p = 0.0003) and well being (p = 0.003) improved more after transdermal estradiol therapy than after placebo. This was also the case for all specific climacteric aspects, including sexual problems (p < 0.0001) and dysfunction (p = 0.01), at comparison with placebo. Self-rated symptom relief was more pronounced with estrogen therapy than with placebo (p < 0.0001).nnnCONCLUSIONnIt was concluded that estradiol therapy was superior to placebo in relieving symptoms and improving quality of life.

Effects of a low-dose desogestrel-ethinylestradiol combination on hirsutism, androgens and sex hormone binding globulin in women with a polycystic ovary syndrome.

Abstract. Twenty women suffering from a polycystic ovary syndrome (PCO) accompanied by hirsutism were given a low‐dose oral contraceptive combination containing 0.150 mg desogestrel plus 0.030 mg ethinylestradiol for 8 months. The pretreatment situation regarding hair and hormone profiles in the PCO group was compared with that in 22 regularly menstruating women. Serum levels of free and total testosterone and androstenedione were significantly elevated in PCO women, as were body weight, blood pressure, hair diameter and depilation frequency. Sex hormone binding globulin (SHBG) binding capacity was lower. Following treatment of the PCO group for 8 months, total and free testosterone levels were depressed, but androstenedione had not changed significantly. SHBG binding capacity was increased five‐fold. Body weight decreased in the obese women. Hair growth was significantly suppressed and the hair itself was less coarse. Depilation intervals were longer. Acne, present before the treatment had now disappeared. Blood pressure did not change. Few and mild side effects were recorded. After treatment, 3 women succeeded in becoming pregnant and in 8 others spontaneous menstruations had recurred.

Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1.

Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.

Estrogen-Progestogen Replacement in Climacteric Women, Particularly as Regards a New Type of Continuous Regimen

Abstract. Twenty‐six peri‐ and postmenopausal women were treated with daily dose of 2 mg 17‐β‐estradiol, 1 mg estriol and 1 mg norethisterone‐acetate in a continuous regimen for 12 months. Clinical parameters such as vasomotor symptoms, bleeding patterns and histopathology were recorded. Blood samples were collected before, after 3 months and after 12 months of treatment and were analysed for estradiol‐17‐β, estrone, androstenedione in serum and lipoprotein lipids.

Management of hormone replacement therapy: the Swedish experience

OBJECTIVEnTo describe the experience of Swedish physicians in the management of hormone replacement therapy (HRT).nnnMETHODSnA postal questionnaire was sent to a sample of Swedish women aged between 46 and 62 years of age. The sample represented one woman in two from the birth cohorts 1946, 1942, 1938, 1934 and 1930.nnnRESULTSnA total of 5990 women were sent the questionnaire and 4525 (76%) completed and returned it. Of this sample, 21% currently used HRT and a further 20% had used it in the past. A high proportion who continued using HRT derived benefit from it which was reflected in relief from vasomotor symptoms, irritability, insomnia, vaginal dryness and muscle and joint pain. Only 27% of those trying other, non-hormonal therapy considered that they had benefited from it. The major reasons for not taking HRT was fear of side-effects, a belief that the menopause should not be interfered with, and at the recommendation of their physician. The same reasons were given by those women starting HRT but discontinuing it later.nnnCONCLUSIONSnThe figure of 21% using HRT compares favourably with other Scandinavian countries. A high proportion of HRT is prescribed by gynaecologists reflecting that many GPs were unfamiliar with its use. When HRT is given by GPs, many favour the transdermal route. Compliance is a major problem and few women continue long enough to benefit fully. One way of minimizing this is to ensure that patients are fully informed and have any fears and misconceptions dealt with. Adverse and misleading information from the media may have to be countered. Individualization of therapy is important and should be tailored to particular age groups. Transdermal HRT may be more acceptable in some cases.

Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456].

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 ± 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.

Lipid metabolic studies in women with a polycystic ovary syndrome during treatment with a low-dose desogestrel–ethinylestradiol combination

Abstract. Twenty women with the polycystic ovary syndrome (PCO) were treated with a combination of deso‐gestrel and ethinylestradiol (EE) and the effects on lipids and lipoproteins were compared with those induced in a group of 13 regularly menstruating, healthy women. All women were examined before and after 3 months of treatment. Compared with the regularly menstruating women, the PCO women had significantly higher body weights and blood pressure as well as elevated levels of triglycerides in serum and VLDL. During treatment, 14 out of 20 women affected by PCO lost weight. No significant change in blood pressure was observed. In the PCO group, moderate increments were encountered in serum cholesterol, phospholipids and triglycerides. No significant changes were seen in LDL‐cholesterol or HDL‐cholesterol. The ratio LDL‐chol‐esterol/HDL‐cholesterol did not alter. The level of total cholesterol in VLDL rose during treatment. These changes in serum and lipoprotein lipids in PCO patients were of the same type and magnitude as those found in the control group, apart from an increase in HDL‐cholesterol in the latter. The only remaining difference after treatment was a slightly higher level of VLDL triglycerides in the PCO women. Thus only moderate changes were induced in lipid and lipoprotein patterns by the combination of desogestrel and EE. A “positive” influence on lipids and lipoproteins cannot be considered as a further advantage, added to the list of indications when hormonal treatment is used in PCO‐af‐fected women. The clinical implications of elevated triglycerides remain to be clarified.

Some aspects of the relationship between oral contraceptives, lipid abnormalities, and cardiovascular disease.

Most epidemiologic studies suggest an association between current use of combined oral contraceptives and certain manifestations of cardiovascular disease. Most of the data relate to older preparations little used today. Decreased levels of high-density lipoprotein cholesterol and increased amounts of low-density lipoprotein cholesterol were common findings with the older formulations. More recent experimental and epidemiologic data suggest that the potential risk of cardiovascular disease in oral contraceptive users is hardly predicated on an arteriosclerosis basis but related more to thromboembolic events. Because changes in the serum lipid profile are often associated with alterations in the factors of hemostasis, it seems reasonable to suggest the use of preparations void of profound changes in lipid metabolism, especially when other means of efficacy are available inclusive of the newer low-dose oral contraceptives. When risk factors for cardiovascular disease are present, determination of total cholesterol is desirable. In subjects with elevated serum cholesterol, a serum lipid profile should be determined. A woman at risk of cardiovascular disease should be carefully monitored, and repeated lipid determinations are recommended.

Ethinylestradiol and Desogestrel, Alone or in Combination with two Doses of Estriol: Effects on plasma proteins

Abstract. Nineteen fertile women were treated with three differently composed oral contraceptives in a cross‐over study and were randomly allocated to begin with one of the three preparations The tablets contained 0030 mg ethinylestradiol + 015 mg desogestrel alone (A) or in Combination with either 05 mg estriol (B) or 2 mg estriol (CI After two treatment cycles on each preparation, blood samples were obtained and analysed for ceruloplasmin, SHBG, prealbumin, transcortin and thyroxine‐binding globulin No differances were found in the induction of liver protein synthesis It was concluded that the addition of estriol in doses of 05 or 2 mg did not influence the effects induced by ethinylestradiol.