Estrogens in the Post-Menopause. Front. Hormone Res., vol. 3, pp. 150-176 (Karger, Basel 1975)
Effects of Oestrogen and Progestogen Therapy on Calcium Metabolism in Post-Menopausal Women J. C. GALLAGHER and Β. Ε. C. NoRDii Medical Research Council Mineral Metabolism Unit, The General Infirmary, Leeds
Introduction In previous publications [GALLAGHER and NoRDIN, 1973, 1974] we have reported that ethínyl oestradiol therapy in post-menopausal women lowers the fasting plasma and urinary calcium and the urinary hydroxyproline, and these observations are in agreement with other workers. ArrΚεκ et al. [1971] showed a similar effect with mestranol and RIGGS et al. [1969] showed the same with conjugated oestrogens. We have found that these effects can also be obtained in post-menopausal women with primary hyperparathyroidism [GALLAGHER and NoRDIi, 1972] and that the effect of oestrogens on calcium balance in these cases is to improve the balance mainly by reducing bone resorption and lowering the urinary calcium [GALLAGHER and WiLkINSON, 1973]. We have also confirmed on a limited number of cases the observation of Arrκεx et al. [1973] that oestrogen therapy inhibits bone loss after the menopause. In the present paper we shall report more detailed observations, both short- and long-term, on the effect of various oestrogens on calcium metabolism in post-menopausal women, and a few observations with progestogens.
All plasma and urine samples were collected after an overnight fast from 8 p.m. the night before. The urine was collected between 8 and 10 a.m., the overnight urine having previously been discarded. Calcium
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Methods
151
phosphorus and creatíníne were estimated in plasma and urine samples by standard Auto-analyzer techniques as was the urinary hydroxyproline. The control plasma and urine values reported, usually represent the mean of three observations. Phosphate reabsorption in the urine was measured by subtracting phosphate excretion (mg/100 ml GF) from plasma phosphate (mg/100 ml). Calcium balances were performed by the dally balance technique described by BULLAMORB et al. [1970], using polyethylene glycol as the nonabsorbable marker [WlLKiisoN, 1971]. Bone turnover was measured with intravenously administered radioactive calcium chloride and the bone mineralisation rate was calculated by the method of Buτκιxsεmω et al. [1969]. Bone resorption rate was calculated as the difference between the mineralisation rate and the calcium balance. Thirteen post-menopausal women had calcium balances on and off ethinyl oestradiol 0.05 mg daily. Six of the patients were normal, four patients had osteoporosis with vertebral crush fractures and three patients had previously suffered from a fractured neck of femur. Metacarpal cortical and total width was measured on six metacarpals in duplicate and the mean values determined by the method of HORsΜλν and NORDIN [1973]. Sequential observations on each individual enabled the mean rate of loss to be determined for normal post-menopausal women, and compared to that in women on oestrogens. Vaginal smears were stained by the Papanicolaou method and the maturation index calculated by the method of STONE et al. [1967]. Four different oestrogen preparations have been given to the patients. Oest ol dihemisuccinate (Synapause) was given to eight patients in doses of 2, 4, 6 and 8 mg; each dose was given for 1 month before being increased. At the end of this study seven of the patients were then given ethinyl oestradiol 0.025 mg and followed up to 6 months. Five other patients who have taken ethinyl oestradiol 0.025 mg only were included in the results on this dose. Ethinyl oestradiol 0.05 mg daily was given to 25 post-menopausal women, three patients having now completed 2 years, two patients 3 years, and three patients have been on therapy for 5 years. Oestrone sulphate (Harmogen) has been given to eight patients; for the first month they took 1 mg daily and then the dose was increased to 2 mg which they took for 3 months. Conjugated oestrogens (Premarin) have been given to seven patients; for the first month they took 0.65 mg dally and then the dose was increased to 1.25 mg daily for 3 months. This latter study is still in progress.
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Downloaded by: Université de Paris 193.51.85.197 - 1/19/2020 6:32:13 PM
Fig. 1. The effect of ethinyl oestradiol 0.05 mg daily on fasting plasma calcium in post-menopausal women. Fig. 2. The effect of ethinyl oestradiol 0.05 mg daily on fasting urine calcium/ creatinine (Ca/Cr) in post-menopausal women.
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Effects of Oestrogen and Progestogen Therapy
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4 Fig. 3. The effect of ethinyl oestradiol 0.05 mg dally on fasting plasma phosphate in post-menopausal women. Fig. 4. The effect of ethinyl oestradiol 0.05 mg daily on the fasting urine phosphorus/ creatinine in post-menopausal women.
Results
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Ethinyl Oestradiol 0.05 mg Daily Plasma and urine calcium. The effect of ethinyl oestradiol 0.05 mg on fasting plasma calcium is shown in figure 1. The mean control value was 9.86 mg/100 ml and it fell at 1 month to 9.45 mg/100 ml (p
Effects of Oestrogen and Progestogen Therapy on Calcium Metabolism in Post-Menopausal Women J. C. GALLAGHER and Β. Ε. C. NoRDii Medical Research Council Mineral Metabolism Unit, The General Infirmary, Leeds
Introduction In previous publications [GALLAGHER and NoRDIN, 1973, 1974] we have reported that ethínyl oestradiol therapy in post-menopausal women lowers the fasting plasma and urinary calcium and the urinary hydroxyproline, and these observations are in agreement with other workers. ArrΚεκ et al. [1971] showed a similar effect with mestranol and RIGGS et al. [1969] showed the same with conjugated oestrogens. We have found that these effects can also be obtained in post-menopausal women with primary hyperparathyroidism [GALLAGHER and NoRDIi, 1972] and that the effect of oestrogens on calcium balance in these cases is to improve the balance mainly by reducing bone resorption and lowering the urinary calcium [GALLAGHER and WiLkINSON, 1973]. We have also confirmed on a limited number of cases the observation of Arrκεx et al. [1973] that oestrogen therapy inhibits bone loss after the menopause. In the present paper we shall report more detailed observations, both short- and long-term, on the effect of various oestrogens on calcium metabolism in post-menopausal women, and a few observations with progestogens.
All plasma and urine samples were collected after an overnight fast from 8 p.m. the night before. The urine was collected between 8 and 10 a.m., the overnight urine having previously been discarded. Calcium
Downloaded by: Université de Paris 193.51.85.197 - 1/19/2020 6:32:13 PM
Methods
151
phosphorus and creatíníne were estimated in plasma and urine samples by standard Auto-analyzer techniques as was the urinary hydroxyproline. The control plasma and urine values reported, usually represent the mean of three observations. Phosphate reabsorption in the urine was measured by subtracting phosphate excretion (mg/100 ml GF) from plasma phosphate (mg/100 ml). Calcium balances were performed by the dally balance technique described by BULLAMORB et al. [1970], using polyethylene glycol as the nonabsorbable marker [WlLKiisoN, 1971]. Bone turnover was measured with intravenously administered radioactive calcium chloride and the bone mineralisation rate was calculated by the method of Buτκιxsεmω et al. [1969]. Bone resorption rate was calculated as the difference between the mineralisation rate and the calcium balance. Thirteen post-menopausal women had calcium balances on and off ethinyl oestradiol 0.05 mg daily. Six of the patients were normal, four patients had osteoporosis with vertebral crush fractures and three patients had previously suffered from a fractured neck of femur. Metacarpal cortical and total width was measured on six metacarpals in duplicate and the mean values determined by the method of HORsΜλν and NORDIN [1973]. Sequential observations on each individual enabled the mean rate of loss to be determined for normal post-menopausal women, and compared to that in women on oestrogens. Vaginal smears were stained by the Papanicolaou method and the maturation index calculated by the method of STONE et al. [1967]. Four different oestrogen preparations have been given to the patients. Oest ol dihemisuccinate (Synapause) was given to eight patients in doses of 2, 4, 6 and 8 mg; each dose was given for 1 month before being increased. At the end of this study seven of the patients were then given ethinyl oestradiol 0.025 mg and followed up to 6 months. Five other patients who have taken ethinyl oestradiol 0.025 mg only were included in the results on this dose. Ethinyl oestradiol 0.05 mg daily was given to 25 post-menopausal women, three patients having now completed 2 years, two patients 3 years, and three patients have been on therapy for 5 years. Oestrone sulphate (Harmogen) has been given to eight patients; for the first month they took 1 mg daily and then the dose was increased to 2 mg which they took for 3 months. Conjugated oestrogens (Premarin) have been given to seven patients; for the first month they took 0.65 mg dally and then the dose was increased to 1.25 mg daily for 3 months. This latter study is still in progress.
Downloaded by: Université de Paris 193.51.85.197 - 1/19/2020 6:32:13 PM
GALLAGHER/NORDIN
152
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Most of the patients treated with oestrogens had undergone hysterectomy and bilateral oophorectomy, and in this group oestrogens were given every day; otherwise the `natural menopause' ,patients were given cyclical oestrogens, 3 weeks on therapy followed by a week off.
Downloaded by: Université de Paris 193.51.85.197 - 1/19/2020 6:32:13 PM
Fig. 1. The effect of ethinyl oestradiol 0.05 mg daily on fasting plasma calcium in post-menopausal women. Fig. 2. The effect of ethinyl oestradiol 0.05 mg daily on fasting urine calcium/ creatinine (Ca/Cr) in post-menopausal women.
Plasma phosphate, mg /100m1
Effects of Oestrogen and Progestogen Therapy
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153
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3.0
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4 Fig. 3. The effect of ethinyl oestradiol 0.05 mg dally on fasting plasma phosphate in post-menopausal women. Fig. 4. The effect of ethinyl oestradiol 0.05 mg daily on the fasting urine phosphorus/ creatinine in post-menopausal women.
Results
Downloaded by: Université de Paris 193.51.85.197 - 1/19/2020 6:32:13 PM
Ethinyl Oestradiol 0.05 mg Daily Plasma and urine calcium. The effect of ethinyl oestradiol 0.05 mg on fasting plasma calcium is shown in figure 1. The mean control value was 9.86 mg/100 ml and it fell at 1 month to 9.45 mg/100 ml (p
