1 University of Bristol, Division of Obstetrics and Gynaecology, St Michael's Hospital, Bristol and 2 Division of Medicine, Bristol Royal Infirmary, Bristol, UK
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Abstract |
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Key words: hyperprolactinaemia/lipoprotein profile
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Introduction |
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Materials and methods |
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Venous blood collection
All participants had fasting venous blood samples taken on two occasions, timed 7 days apart (during the follicular phase of the menstrual cycle, in the case of the controls) for measurement of plasma total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol and triglyceride concentrations. Mean values were calculated for each participant. Serum prolactin and oestradiol were assayed on the first sample only.
Nine of the patients were treated effectively with bromocriptine resulting in suppression of prolactin levels usually to normal and restoration of ovarian function and menstrual cycles. Blood sampling was repeated on two occasions during the follicular phase after at least 8 weeks of therapy. The other six patients declined bromocriptine therapy and did not have any further blood samples taken for this study.
Lipoprotein and hormone analysis
Lipoproteins were fractionated by a combination of precipitation and micro-ultracentrifugation (Fehily et al., 1988). Briefly, apoprotein-B containing lipoproteins were precipitated using sodium phosphotungstate/magnesium chloride, and high density lipoprotein (HDL) cholesterol in the supernatant was then measured. Very low density lipoprotein (VLDL) was isolated from plasma by ultracentrifugation in a Beckman Airfuge for 3.5 h at 150 000 g. Cholesterol and triglycerides were measured using Boehringer Mannheim kits (236691 and 644200 respectively) [Boehringer Mannheim (UK), Lewes, UK]. Low density lipoprotein (LDL) cholesterol was calculated by difference. All other chemicals were from Sigma Chemical Co., Poole, UK and BDH, Poole, UK. Interassay coefficients of variation were total cholesterol 1.7%, HDL cholesterol 3.1%, LDL cholesterol 2.5% and total triglycerides 7.6%.
Prolactin was assayed by a radio-immunometric method standardized against the WHO 3rd IRP 84/500 using a kit supplied by Medgenix Diagnostics (Fleurus, Belgium). Inter- and intra-assay coefficients of variation for the prolactin assay were 4 and 7% respectively. Oestradiol was estimated by DELFIA immunoassay system (UK distributor Wallac, Milton Keynes). The coefficient of variation was 5.9% at a level of 860 pmol/l, 5.0% at a level of 2500 pmol/l and 6.2% at a level of 5000 pmol/l. Within batch coefficient of variation was less than 5% at all levels.
Statistical analysis
Results were compared statistically by Wilcoxon matched pairs testing.
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Results |
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Discussion |
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However, in the hyperprolactinaemic patients who were effectively treated with bromocriptine there was a significant reduction in total cholesterol and LDL cholesterol levels and smaller changes in the other lipoprotein fractions, all towards the normal control values. We believe this to be the first report of such an effect. Pelkonen et al. (1982) reported no change in the lipoprotein profile in 12 hyperprolactinaemic women studied before and after pituitary surgery, but only seven of these subjects achieved normal or near normal prolactin levels with return of menstrual function.
It was important to establish normal thyroid function in the hyperprolactinaemic group. Hyperprolactinaemia is associated with primary and subclinical hypothyroidism (Semple et al., 1983; Olive and Hennessey, 1988
) which are in turn associated with increased levels of total cholesterol, LDL cholesterol and HDL cholesterol (Muls et al., 1984
; Friis et al., 1987; Kung et al., 1995
). However, in this group of patients, the concentrations of thyroid stimulating hormone (TSH) were normal.
The most likely explanation for the beneficial alterations which we found in the lipoprotein profile following effective dopamine agonist therapy, is the alleviation of oestrogen deficiency as a consequence of return of ovarian function. Oestrogen deprivation, as occurs following bilateral oophorectomy or the natural menopause, is associated with increases in total cholesterol, LDL cholesterol and triglycerides and a reduction of HDL cholesterol (Matthews et al., 1989; Farish et al., 1990
; Stevenson et al., 1993
). Exogenous oestrogen therapy lowers plasma concentrations of total cholesterol and LDL cholesterol and raises HDL cholesterol (Bush et al., 1987
; Walsh et al., 1991
).
Surgical or natural menopause leads to an increased incidence of coronary heart disease (Oliver and Boyd 1959; Sznajderman and Oliver 1963
; Gordon et al., 1978
), which is markedly reduced by oestrogen replacement therapy (Hunt et al., 1990
; Henderson et al., 1991
; Stampfer et al., 1991
). It is believed that changes in lipids and lipoproteins associated with the oestrogen deficient state are at least partially responsible for the increased cardiovascular risk. These changes may influence atheromatous plaque formation and regression. It is likely that hyperprolactinaemic amenorrhoeic women are also at increased cardiovascular risk because of their oestrogen deficiency. They should be encouraged to take effective dopamine agonist therapy, not only to protect them against osteoporosis but to improve their lipoprotein profile and potentially reduce their cardiovascular risk. Alternatively, oestrogen replacement therapy could be considered. Further studies to compare changes in the lipoprotein profile in response to dopamine agonist versus oestrogen replacement therapy would be of interest. However, one has to be mindful of the potential risks of stimulation of prolactin secretion (Fahy et al., 1992
) and pituitary tumour growth (Gooren et al., 1988
; Bevan et al., 1989
; Fahy et al., 1992
) when using oestrogen replacement therapy in such women.
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Acknowledgments |
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Notes |
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References |
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Submitted on March 12, 1998; accepted on October 27, 1998.