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Claus Hagen, Claus Christiansen, Merete Sanvig Christensen and Ib Transbøl


Plasma prolactin (Prl) and follicle stimulating hormone (FSH) concentrations were determined in 196 normal post-menopausal women, aged 45–54 years, receiving different doses of oestrogens in combination with gestagen (28 day cycle) in a placebo-controlled trial. In experiment I, 15 women received trisequens forte for 3 years, 19 women the same hormone combination for 2 years followed by 1 year's placebo treatment, and 15 women received placebo for 3 years. In experiment II, 30 women received trisequens forte, 22 women trisequens, 23 women trisequens mite, 20 women trisequens without oestriol, and 42 women placebo for 1 year. In both studies plasma concentrations of Prl and FSH were measured with 3 to 6 months interval.

The mean plasma Prl concentration increased about 25% (P < 0.01) in all hormone treated groups in both experiments within 1 year's treatment. However, only 26/139 (19%) of the hormone treated women had elevated Prl levels (> 20 μg/l) after 1 year of treatment. The elevated mean plasma Prl levels were maintained throughout the second and the third year of treatment with a trend to further increase. Initially, 6/196 (3.1%) of the post-menopausal women had plasma Prl concentrations of 21–40 μg/l. After 3 years of hormone therapy, 5/15 (33%) had plasma Prl concentrations of 21–60 μg/l. A significant and clearly dose-related fall in the plasma FSH concentration occurred in the hormone treated groups. The decrease varied between 40% and 75% and was seen within the first 3 months of treatment. No significant changes occurred in the mean plasma concentrations of FSH and Prl in the placebo groups.

It is concluded that hormone substitution with cyclical oestrogen/gestagen induces a rise in plasma Prl concentration, which is not related to the dose of oestrogens; and a fall in plasma FSH concentration, which is doserelated. Furthermore, it is suggested that oestriol has no significant Prl stimulating effect.

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Henning Djursing, Claus Hagen, Jan Møller and Claus Christiansen


The physiological changes in plasma prolactin concentration were studied in 447 normal subjects, including 65 men, 75 pre-menopausal women and 307 post-menopausal women. The within-day and day-to-day variation as well as the circadian and circannual rhythm of plasma prolactin levels were determined. Furthermore, the relationship between changes in prolactin and oestradiol-17β levels during the normal menstrual cycle and in the climacteric was studied.

Pre-menopausal women had significantly (P<0.01) higher basal plasma prolactin concentration than men and post-menopausal women. Furthermore, they had significantly (P < 0.01) higher day-to-day variation than men. This suggests that prolactin in women is secreted in a pulsatile fashion. Only small seasonal variations in both sexes were seen.

The levels of plasma prolactin during the ovulatory and the luteal phase in the cycle were significantly (P < 0.02) higher than that of the follicular phase, and a positive correlation between changes in plasma concentration of oestradiol-17β and prolactin was found. Also in post-menopausal women a relationship between plasma concentration of prolactin and oestradiol-17β was seen.

It is concluded that the assessment of prolactin concentration in blood is dependent on the physiological variation recorded during sleep in both sexes. However, only in women day-to-day changes and the changes related to the menstrual cycle and the climacteric are of importance.

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Dorthe Hartwell, Christian Hassager and Claus Christiansen

Abstract. Serum concentrations of vitamin D2 and vitamin D3 metabolites were measured in 19 normal subjects before and during treatment with either vitamin D2 or vitamin D3, 4000 IU per day for 8 weeks. Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. During treatment with vitamin D3, the serum concentration of 1,25(OH)2D metabolites was unchanged. We conclude that the production of 1,25(OH)2D is tightly regulated and that 1α-hydroxylase does not discriminate between D2 and D3 metabolites in normal subjects.

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Julia S. Johansen, J. E. Mølholm Hansen and Claus Christiansen

Abstract. To study the value of bone Gla protein (BGP) as a biochemical marker of normal bone physiology and metabolic bone disorders, we have developed a radioimmunoassay (RIA) for the detection of BGP in human plasma. Antibodies were generated in rabbits immunized with purified calf BGP conjugated to thyroglobulin. Human plasma BGP reacted identically with the calf BGP standard, thus demonstrating the suitability of the assay to measure plasma BGP levels in man. The RIA is sensitive, accurate, and technically simple. Plasma BGP levels were determined in normal subjects (N = 35) and in patients with hypothyroidism (N = 10), hyperthyroidism (N = 22) and chronic renal failure (N = 35). The mean (± 1 sem) concentration of plasma BGP in normal subjects was 1.27 ± 0.07 nmol/l. Plasma BGP was significantly increased in patients with hyperthyroidism, 4.04 ± 0.78 nmol/l (P < 0.001) and chronic renal failure, 10.17 ± 2.47 nmol/l (P < 0.001). Low concentrations were found in patients with hypothyroidism, 0.74 ± 0.11 nmol/l (P <0.01). Our studies indicate that plasma BGP provides a useful technique in the diagnosis of patients with bone disease.

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Lone Tjellesen, Claus Christiansen, Lotte Hummer and Niels-Erik Larsen


To examine the effect of endogenous oestrogens on calcium metabolism during the menstrual cycle, fasting blood and urinary samples were obtained every day throughout the menstrual cycle in 5 young women.

Bone turnover was estimated by serum alkaline phosphatase and fasting urinary excretions of hydroxyproline and calcium. Serum levels of oestradiol (E2), oestrone (E1), and androstenedione (A) showed the well known cyclic fluctuations, the serum 1,25-dihydroxyvitamin D (1,25(OH)2D) nearly doubled from the early follicular phase to the time of ovulation, although 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were almost unchanged. No correlation between the rise in the serum 1,25(OH)2D level and the measured parameters of calcium metabolism was observed.

In view of these findings, the 1,25(OH)2D3 serum concentration measured in women with functioning ovaries can only be interpreted in the context of the menstrual cycle. The published normal range in women for the metabolite may also require reinterpretation.

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Kirstine Stochholm, Svend Juul, Jens Sandahl Christiansen and Claus Højbjerg Gravholt


Childhood onset GH deficiency (CO-GHD) is associated with increased morbidity and mortality; however, the patients' socioeconomic profile as adults is not fully known.


Register study using Danish nationwide registries. Two hundred and sixty GHD males and 156 GHD females and 25 358 male and 15 110 female controls were included.


Information was obtained concerning cohabitation, parenthood, education, income, retirement, convictions, and death. Income was analyzed using conditional logistic regression, and other outcomes were analyzed using Cox regression. Subgroups of GHD patients with malignant tumors, craniopharyngioma, idiopathic GHD, and others were investigated separately.


Both male and female GHD patients had a significantly worse outcome on all studied socioeconomic parameters. Fewer GHD patients lived in partnerships and entered them later (male hazard ratio (HR): 0.31; female HR: 0.33), had fewer parenthoods (male HR: 0.26; female HR: 0.26), lower educational level (male HR: 0.58; female HR: 0.48), lower income, higher risk of retirement (male HR: 13.4; female HR: 24.2), and fewer convictions (male HR: 0.67; female HR: 0.49). Mortality was increased (male HR: 10.7; female HR: 21.4). Adjusted for marital and educational status, male HR of death was 5.2 and female HR 10.5. Patients with idiopathic GHD had a socioeconomic profile similar to controls.


The primary causes of CO-GHD and concomitant diseases severely impair socioeconomic conditions and impact mortality; only the subgroup of patients with idiopathic GHD conditions was similar to the background population.

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Jens J Christiansen, Jens M Bruun, Jens S Christiansen, Jens Otto Jørgensen and Claus H Gravholt


Adrenal derived androgens are low in women with adrenal failure. The physiological consequences of substitution therapy are uncertain.


To investigate the effects of DHEA substitution in women with adrenal failure on body composition, fuel metabolism, and inflammatory markers.

Design, participants and intervention

In this study, ten female patients (median age 38.5 years, range 28–52) with adrenal failure were treated with DHEA 50 mg for 6 months in a double-blind, randomized, placebo-controlled, and crossover study. The participants underwent dual-energy X-ray absorptiometry (DXA) scan, computed tomography scan of abdominal fat, indirect calorimetry, bicycle ergometry, muscle and fat biopsies, and blood samples.


Baseline androgens were normalized to fertile range during active treatment. Anthropometric data were unaffected, but lean body mass (LBM) slightly increased compared with placebo (delta LBM (kg) placebo versus DHEA: −0.48±6.1 vs 1.6±3.4, P=0.02) with no alterations in total or abdominal fat mass. PTH increased with DHEA, but no significant changes were observed in other bone markers or in bone mineral content. The mRNA levels of markers of tissue inflammation (adiponectin, interleukin 6 (IL6), IL10, monocyte chemoattractant protein 1, and tumor necrosis factor α) in fat and muscle tissue were unaffected by DHEA treatment, as was indirect calorimetry and maximal oxygen uptake. A high proportion of self-reported seborrheic side effects were recorded (60%).


In female adrenal failure, normalization of androgens with DHEA 50 mg for 6 months had no effects on muscle, fat, and bone tissue and on fuel metabolism in this small study. A small increase in LBM was observed. Treatment was associated with a high frequency of side effects.

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Dorthe Hartwell, Christian Hassager, Kirsten Overgaard, Bente Juel Riis, Jan Pødenphant and Claus Christiansen


We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

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Annette Schlemmer, Christian Hassager, Juha Risteli, Leila Risteli, Signe B Jensen and Claus Christiansen

In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.

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Claus Højbjerg Gravholt, Henrik Enghusen Poulsen, Peter Ott, Jens Sandahl Christiansen and Hendrik Vilstrup

Background: Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.

Aim: To study quantitative liver functions in TS in detail with and without HRT.

Design: Randomized crossover study with active treatment (HRT in TS and P-pill in controls) or no treatment.

Subjects: Women with TS (n = 8, age 29.7 ± 5.6 (mean ± s.d.) years), verified by karyotype, and age-matched controls (C; n = 8, age 27.3 ± 4.9 years).

Methods: We determined liver enzymes in blood, used the galactose elimination capacity to assess hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, antipyrine clearance to estimate microsomal activity, and the functional hepatic nitrogen clearance (FHNC) to assess mitochondrial-cytosolic metabolic capacity for conversion of amino-nitrogen.

Results: Liver enzymes were elevated in untreated TS and reduced by HRT. The hepatic capacities for conversion of galactose, indocyanine green, and antipyrine were normal and did not change by HRT. The FHNC was marginally reduced (untreated TS vs C: 19.4 ± 5.4 vs 25.2 ± 7.3 L/h, P = 0.1). FHNC changed slightly with HRT in TS (19.4 ± 5.4 vs 24.4 ± 10.2 L/h, P = 0.2).

Conclusions: The elevations of liver enzymes in untreated TS are readily suppressed by HRT. Quantitative liver functions in TS are comparable to controls and are not affected by HRT.