A review of study findings of the risks and benefits of oestrogen therapy in the female climacteric.

A literature review was conducted to assess the evidence regarding the risks and benefits of oestrogen therapy in climacteric women. Consideration was given to the route of administration, effects on lipid levels, the skin and urinary symptoms, endometrial cancer, mortality and replacement therapy. It was concluded from the data examined that properly administered oestrogen treatment does not increase the risk of endometrial cancer and that the relative risk of death in oestrogen users aged over 40 is markedly lower than than in non-users.

Supravaginal uterine amputation with peroperative electrocoagulation of endocervical mucosa. Description of the method.

Discussion on the advantages of abdominal hysterectomy versus supravaginal uterine amputation has concentrated on the incidence of carcinoma in the remaining stump, mortality, and other serious complications. During the period 1952-78 we have performed 2712 supravaginal amputations with peroperative electrocoagulation of endocervical mucosa. The incidence of stump carcinoma was 0.11% in this material. In our prospective studies we have shown that supravaginal amputation has certain advantages over abdominal hysterectomy as regards long-term morbidity. In this paper we describe the method we are using when performing supravaginal uterine amputation.

Effect of prostaglandin inhibitor and oestrogen on climacteric symptoms and serum free fatty acids.

Oestradiol and naproxen were compared in a double-blind, cross-over study of 20 women suffering from climacteric symptoms. Subjective symptoms were assessed before and after treatment. In addition, serum levels of prostaglandin precursors and of certain other free fatty acids were determined. Oestradiol was found to have a slightly more pronounced effect than naproxen on symptoms and on fatty acid levels. Nevertheless, a large number of the patients reported significant alleviation of their symptoms on naproxen. Some of the climacteric symptoms may thus be mediated by prostaglandins. In most patients the fatty acid levels decreased after treatment with both substances, but there were two exceptions. It is suggested that there may be two separate types of metabolic response to these drugs.

Skinfold thickness and long-term post-menopausal hormone therapy.

Skinfold thickness was measured in 130 post-menopausal women treated with long-term hormone therapy. One group of 50 women took oestradiol valerate 2 mg/day for 3 wk out of 7, a second group comprising 19 women received oestriol succinate 2 mg/day and the remaining group of 61 women used oestradiol valerate 2 mg/day combined sequentially with norgestrel 0.5 mg/day. The duration of treatment in these groups was 6.3 +/- 0.4, 6.4 +/- 0.4 and 3.3 +/- 0.3 yr, respectively. The control group was made up of a further 89 post-menopausal women. The skinfold thickness in all the treated groups was significantly greater than that in the controls.

Long-term post-menopausal hormone therapy and serum HDL-C, total cholesterol and triglycerides.

Serum high-density lipoprotein cholesterol (HDL cholesterol), total cholesterol and triglyceride concentrations were determined in 158 post-menopausal women following long-term oral hormone replacement therapy. Oestradiol valerate (2 mg/day) was taken by 53 of the women and oestriol succinate (2 mg/day) by 42 others. The duration (means +/- SD) of the oestradiol valerate therapy was 6.4 (+/- 2.9) yr and of the oestriol succinate therapy 6.4 (+/- 2.3) yr. The remaining 63 women received oestradiol valerate (2 mg/day) combined sequentially with norgestrel (0.5 mg/day). The average duration of treatment with this combination was 3.3 (+/- 2.4) yr. The control group comprised 100 post-menopausal women who received no hormone therapy whatsoever. The HDL cholesterol levels in the women receiving oestradiol valerate were higher than those in the controls (P = 0.001) and in the women on oestradiol valerate plus norgestrel therapy (P less than 0.001). The HDL cholesterol levels in the oestriol succinate group did not differ significantly from those in the controls. The women receiving oestradiol valerate in combination with norgestrel had lower serum HDL cholesterol concentrations than the controls (P less than 0.05). Serum total cholesterol and triglyceride concentrations did not differ in either oestrogen group from those in the controls, but were lower in the oestradiol valerate-plus-norgestrel group than in the controls (P less than 0.001). There were no differences in serum total oestrogen, oestrone, oestradiol and oestriol levels between control subjects with normal HDL cholesterol concentrations and those with low concentrations.

Supravaginal uterine amputation vs. hysterectomy. Effects on libido and orgasm.

Postoperative symptoms of hysterectomy have received relatively little attention. In the present study, the first author has personally interviewed and examined 105 abdominal hysterectomy patients and 107 patients with supravaginal uterine amputation preoperatively and 6 weeks, 6 months and 12 months postoperatively. Participation in the follow-up study was 99.5% (211/212) at one year. This paper deals with the effects of the two operations on libido and the frequency of orgasms. In the statistical analysis, McNemar's test of symmetry and the Fisher exact test were used. Weak or absent libido was reported preoperatively by 28.0% of hysterectomy patients and by 26.4% of amputation patients. One year postoperatively the corresponding figures were 35.4% and 31.4%. No statistical changes were observed between the two groups or within either group. In the frequency of orgasms a highly significant (p less than 0.001) reduction from the situation before operation to one year postoperatively was detected after hysterectomy. In the supravaginal amputation group no statistically significant decrease was detected. Preoperatively the two groups were alike; one year postoperatively the difference was almost significant (p less than 0.05). The reductions in orgasms after hysterectomy as compared with supravaginal amputation appears to result from the greater radicality of the former; at hysterectomy, the autonomous innervation of the proximal vagina and cervix is damaged more than in supravaginal amputation, the anatomy of the vagina is altered and scar tissue forms in the vagina. It is probable that these changes and subconscious psychological reactions due to total removal of the uterus explain why supravaginal uterine amputation gives better results than hysterectomy.

Bilateral oophorectomy and plasma renin substrate concentration.

Plasma renin substrate concentration was studied in 11 premenopausal women subjected to bilateral oophorectomy and hysterectomy. Preoperative plasma renin substrate concentration was 1573 +/- 477 ng angiotensin I/ml (mean +/- SD). Plasma renin substrate concentration did not change significantly after operation (1632 +/- 459 ng angiotensin I/ml) or after 3 months of postoperative estradiol valerate treatment (2 mg/day) (1762 +2- 467 ng angiotensin I/ml). It is concluded that non-pregnant levels of endogenous estrogens are of no significance in the regulation of plasma renin substrate.

Monitoring perinatal mortality by birth weight specific mortality rates.

The perinatal mortality at University Central Hospital of Turku, Finland decreased significantly from 15.7/1000 in years 1970-75 to 8.9/1000 in years 1976-78. The main decrease has occurred in weight groups of 1000 g and more. In years 1976-78 the perinatal mortality of non-malformed babies in the weight group 1500-1999 g was 93/1000, in the group 2000-2499 g 21/1000 and in the group of 2500 g and over 1.7/1000. The early neonatal mortality of non-malformed infants has decreased significantly only in the weight group of 1500-1999 g. The 1-week survival rate has been 48% in the weight group 500-999 g, but 77% in the weight group 1000-1499 g. The birth weight specific mortality rates are greatly required when the quality of obstetrical care is assessed. Birth weight specific neonatal mortality rates are essential when guidelines for elective termination of third trimester pregnancy are designed.

Conservative treatment of urinary incontinence in women with special reference to the use of oestrogens.

Urinary incontinence was treated conservatively in 100 patients. The follow-up period was 12-24 mth. For post-menopausal women, the oestrogen therapy consisted of oral oestradiol valerate or vaginal oestrone sulphate combined with emepronium bromide. In post-menopausal patients the best results were noted when incontinence had begun at the menopause and when the duration of the complaint was not more than 3 yr. For pre-menopausal patients, the treatment given was generally emepronium bromide. During the follow-up period 15 of the patients, 11 of whom were post-menopausal, became symptomless and 77 improved; that is, the incontinence was only slight and occasional. The treatment was without any effect in 8 of the patients. Oestrogen therapy was successful in most post-menopausal women. In these patients, the best results were obtained when the duration of the incontinence was not more than 3 yr.

Serum concentrations of oestrone, oestradiol and oestriol during various oestrogen treatments.

Serum oestradiol/oestrone ratios were measured during various oestrogen treatments in castrated women. Oral oestriol succinate therapy (8 mg/day) caused little change in the pre-treatment oestradiol/oestrone ratio. During oestradiol valerianate therapy (2 mg/day) serum total oestrogens and the E2/I1 ratio were considerably increased. One day after the injection of 10 mg of oestradiol valerianate and 2.5 mg of oestradiol benzoate + 10 mg of oestradiol phenylpropionate the E2/E1 ratio was similar to the ratio in middle of the normal ovulatory cycle. The change in serum oestriol was rather small after oral doses of 8 mg og oestriol succinate 15, 30 and 120 min after the application.

The first abortion - and the last? A study of the personality factors underlying repeated failure of contraception.

The causes leading to a second abortion were outlined in a psychological study comparing 30 women expecting a second abortion with 29 women who had successfully prevented conception after a first abortion. It was found that both groups improved their contraceptive practices after the first abortion. However, while the latter group continued with their improved practices, the former group went back to the earlier inefficient or non-existent contraceptive behavior. The inability to improve contraception in the long run was not related to differences in educational level or knowledge about contraceptive techniques but to the developmental level of personality structures. The women expecting their second abortion rated lower in control of impulsivity, emotional balance, realism, self-esteem and stability of life as well as capacity for more integrated personal relationships. The differences in personality development and consequently in the capacity for long-term contraception were found to be due to growth conditions in childhood.

The vaginal absorption of oestrogens in post-menopausal women.

Serum E1, E2 and E3 concentrations and E2/E1 ratio were measured after vaginal application of conjugated oestrogens, micronized 17 beta-oestradiol and oestriol. 2.4 mg of conjugated oestrogens caused a prompt elevation in the serum E1 concentration; the E2 level changed only slightly. After vaginal application of 2 mg micronized 17 beta-oestradiol the main serum oestrogen is E2 and the conversion of E2 to E1, as in oral administration, does not occur. A significant elevation in the serum E3 concentration was noted 2 h after the vaginal application of 0.5 mg oestriol. The E2/E1 ratio changed little after the application of conjugated oestrogens but increased considerably after the vaginal administration of 2 mg micronized 17 beta-oestradiol.

Ovarian production of estrogens in postmenopausal women.

We investigated the possible secretory capacity of the ovaries of 79 postmenopausal women with and without endometrial carcinoma using chemical, enzymehistochemical and ultrastructural methods. The mean serum levels of estrone, estradiol and total estrogens were higher in ovarian effluent blood than the corresponding values in cubital venous blood. There was a positive correlation between the difference of total estrogens in ovarian and cubital vein sera and, on the other hand, enzymehistochemical and ultrastructural findings in ovarian tissue. No statistical differences were found in the peripheral mean values of estrone and total estrogens between the two groups. The mean level of estradiol, however, seemed to be higher and that of estriol lower in the carcinoma patients than in the control groups.

Estradiol valerate therapy and the renin--aldosterone system in castrated women.

The effect of estradiol valerate (Progynova, 2 mg daily) on the renin--aldosterone system was studied in nine women after bilateral oophorectomy. Plasma renin activity (PRA) and the daily urinary excretion of aldosterone (dU-Ald) were determined 4 mth after the operation -- during which no estrogen was given -- and after 3 mth on estrogen therapy. Plasma estradiol concentration rose in 7 subjects to the normal postovulatory level. No changes were found in PRA or dU-Ald. The results suggest that an effective estradiol valerate therapy is not accompanied with activation of renin--aldosterone system, while synthetic and non-human natural estrogens (Premarin) were shown earlier to increase PRA.

Endogenous oestrogens and the renin-aldosterone axis--castration of women with high or normal oestradiol level.

Oestrogens increase plasma renin activity (PRA) by inducing synthesis of renin substrate in the liver. This is proved clinically by the synthetic oestrogens of oral contraceptives and by the equine conjugated oestrogens in postmenopausal therapy. The effect of endogenous oestrogen production on the activity of the renin-aldosterone system is not clear, but progesterone is an important stimulus of renin release in the luteal phase of menstrual cycle. We studied 15 premenopausal women undergoing bilateral oophorectomy. Eight women had high mean serum oestradiol level 1.2 +/- 0.6 (SD) nmol/l for follicular cysts or for a prolonged climacteric proliferation phase. Seven women had normal follicular oestradiol level (0.2 +/- 0.1 nmol/l). In PRA or daily urinary aldosterone excretion (dU-Ald) no differences could be found between the groups. In one month after oophorectomy no changes in PRA or dU-Ald were found in either group, while the serum oestradiol fell to unmeasurable levels. The results suggest that endogenous oestrogens are not to cause activation of the renin-aldosterone axis as measured by the clinically useful PRA and dU-Ald. The result is in agreement with previous reports of postmenopausal therapy with oestriol succinate or oestradiol valerate.

The effect of castration and estrogen therarapy on serum high-density lipoprotein cholesterol.

The effect of castration on serum high-density lipoprotein (HDL) cholesterol was studied in 11 women with fairly regular menstruation. The HDL cholesterol levels before and one month after castration did not differ significantly. The effect of intramuscular estrogen therapy on HDL cholesterol was investigated in six castrated women. Ten days after injections of both 10.0 mg of estradiol valerate and 2.5 mg of estradiol benzoate plus 10.0 mg of estradiol phenylpropionate, HDL cholesterol was increased significantly. Fifteen days later, HDL cholesterol levels returned to the pretreatment values.