The effect of estrogen therapy on somatic and psychical symptoms in postmenopausal women.

The effect of oral estrogen replacement therapy upon somatic and psychical disturbances and sexuality was studied in a double-blind investigation in 48 postmenopausal women using hormone preparations with two different levels of micronized estradiol-17 beta (E2) as active estrogen component. The patients were treated for 8 months in four 2-month periods with two preparations containing 1-2 mg of E2 (TrisekvensR and EstrofemR), with one preparation containing 1-4 mg of E2 (TrisekvensR forte) and with a placebo preparation. Investigations performed before and during treatment included general clinical chemical analysis, serum levels of FSH, LH and E2 and evaluation of the patients' somatic and psychical disturbances and sexuality. The patients were classified into three subgroups according to their pretreatment scores for mental distress and/or depression: severe (group I), moderate (group II), or no (group III) mental distress and/or depression. No significant differences between the three subgroups were found in pretreatment values from the general clinical chemical analysis or the hormone assays. Estrogen treatment significantly reduced S-total cholesterol values in all three subgroups; otherwise no significant effects were revealed by the general clinical chemical analysis. During the period of optimal wellbeing, serum E2 levels corresponded to luteal phase values. The gonadotropin levels, although depressed by approx. 50%, were still within the postmenopausal range. There were no significant differences between the two subgroups in hormone levels obtained during optimal estrogen treatment. Twenty-one patients had the best test results when treated with the larger dose (TrisekvensR forte) and 23 with the smaller dose (TrisekvensR and EstrofemR) and 4 during placebo treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravaginal oestrogen treatment upon the vaginal absorption of conjugated equine oestrogens.

Conjugated equine oestrogens (0.625 mg) were administered daily and intravaginally to 7 postmenopausal women (aged 70-93 yr) for 14 days. Blood samples were taken at days 1 and 14 immediately before and 2, 4 and 6 h after oestrogen application and at days 4, 6, 8, 11 and 13, 4 h after application. Serum samples were analyzed with respect to total oestrone (E1), unconjugated 17 beta-oestradiol (E2), FSH and LH. Serum total E1 and E2 increased rapidly at day 1 to luteal and follicular phase levels respectively. After that total E1 levels decreased to a plateau corresponding to follicular phase values and remained at that level throughout the treatment period. Serum E2 remained at the follicular phase level during the entire period of treatment. No increase in serum oestrogens could be detected after oestrogen application at day 14. Serum gonadotrophins were already suppressed at day 4 and further decreased to premenopausal values during the latter half of the treatment period. It is speculated that the effects of oestrogens upon a post-menopausal vaginal mucosa involves a diminished resorption of conjugated oestrogens. This effect is, however, not sufficient to avoid systemic effects at the dosage used.

Hyperprolactinemia in cases of infertility and amenorrhea.

Of 17 patients with longstanding (3--15 years, mean 7.7 years) amenorrhea and hyperprolactinemia, 8 developed their amenorrhea after the use of oral contraceptives (Group I) and 9 became amenorrhoic spontaneously (Group II). There were no differences between the groups with respect to the basal serum levels of FSH, LH, low polar estrogens (estradiol-17 beta + estrone) and prolactin. Tomography revealed pituitary adenoma in four patients. One of these developed symptoms of her tumor during pregnancy; the symptoms disappeared after delivery. The other patients with tumors are checked twice a year and have not yet received any treatment. The patients with no detectable tumors were treated with bromocriptine starting with 1.25 X 3 daily. The peripheral serum levels of prolactin, FSH, LH, low polar estrogens and progesterone were determined once a week and if the prolactin levels remained high, the bromocriptine dose was increased. All these patients started to menstruate as soon as prolactin returned to normal levels (below 25 micrograms/l). All patients who wished to became pregnant, i.e. 6 patients. Three were delivered by cesarean section, one had a normal delivery and two are still pregnant. There was no difference between Group I and Group II in the dose required or in the duration of treatment before menstruation started. Three cases of galactorrhea were found.

PIP: Of 17 patients with longstanding amenorrhea and hyperprolactinemia (3-15 years, mean 7.7 years), 8 developed their amenorrhea after the use of oral contraceptives (Group 1) and 9 became amenorrheic spontaneously (Group 2). There were no differences between the groups with respect to the basal serum levels of (FSH) follicle stimulating hormone; (LH) luteinizing hormone; (LPE) low polar estrogens (estradiol-17 beta and estrone); and prolactin. Tomography revealed pituitary adenoma in 4 patients; 1 developed symptoms of her tumor during pregnancy and they subsided following delivery. The others with tumors are checked twice/year and have not yet received treatment. The patients with no detectable tumors were treated with bromocriptine starting with 1.25x 3 daily. The peripheral serum levels of prolactin, FSH, LH, LPE, and progesterone were determined once a week and if the prolactin levels remained high, the bromocriptine dosage was increased. All patients began to menstruate once the prolactin returned to normal levels (below 25 mcg/l). Those patients who desired to become pregnant (N=6) subsequently did. 3 were delivered by cesarean section, 1 had a normal delivery, and 2 are still pregnant. There were no differences between Group 1 and 2 in the dose required or in the duration of treatment before menstruation started. 3 cases of galactorrhea were found.

Intravaginal administration of conjugated estrogens in premenopausal and postmenopausal women.

Daily doses of 0.625 mg of conjugated estrogens were administered intravaginally for 14 days to 12 postmenopausal women (six with highly atrophic and six with slightly atrophic vaginal mucosa), resulting in vaginal mucosae similar to those found in premenopausal women in all 12 subjects. In a second experiment, serum estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined before and hourly for six hours after a single intravaginal dose of 0.625 mg of conjugated estrogens was given to five postmenopausal women and to five premenopausal women on cycle days 6-8. Serum levels of unconjugated immunoreactive estrogens and total estrone increased rapidly in four of five postmenopausal women. Luteal phase values were found after only two hours, but there were no effects on serum FSH and LH. One of the postmenopausal women who had an unatrophied vaginal mucosa, showed a considerable lower resorption of estrogens. There were no significant changes in the serum estrogen levels of the premenopausal women. Thus, we conclude that daily vaginal administration of 0.625 mg of conjugated estrogens for 14 days is sufficient to restore an atrophic vaginal mucosa to a premenopausal condition. Furthermore, the condition of the vaginal mucosa seems to influence the resorption, thus indicating an inbuilt mechanism of protection against overdosage of intravaginally applied estrogens.

Serum levels of total dehydroepiandrosterone and total estrone in postmenopausal women with special regard to carcinoma of the uterine corpus.

Serum levels of total dehydroepiandrosterone and total estrone were determined in 18 postmenopausal women with carcinoma of the uterine corpus (stage I, grade 1-3) and in 40 healthy postmenopausal women. Elevated levels of both steroids were found in the carcinoma group, for dehydroepiandrosterone 2010+/-195 vs. 1299+/-117 nM, p less than 0.01, and for estrone 2,38+/-0.24 vs. 1.36+/-0.11 nM, p less than 0.001. Dehydroepiandrosterone as well as the precursors of estrone are almost exclusively of adrenal origin in the postmenopausal woman. Thus these findings indicate a role of the adrenal cortex in the etiology of corpus carcinoma, either by providing increased levels of substrate for the peripheral synthesis of estrone or a direct action of adrenal androgens on the endometrial tissue.

Changes in bone mineral content in women with natural menopause during treatment with female sex hormones.

The bone mineral content was determined in eleven women with a natural menopause by X-ray spectrophotometry during treatment with a combinations of estrogens and a gestagen. During a three-year follow-up period the hormone treated women significantly increased (P less than 0.05) their mineral content by 3% a year on average, as compared with a control group. Even in patients who had passed the menopause several years previously, the increase occurred and was particularly great during the first year of treatment.

[Hormone treatment in estrogen deficiency can be as natural as insulin in diabetes]. / Hormonterapi vid östrogenbrist kan vara lika naturligt som insulin vid diabetes

PIP: Estrogen treatment is indicated in cases of climacteric afflictions, which occur in 50-80% of the women in various studies, and in cases where symptoms of lack of estrogen become apparent. Climacteric afflictions such as vasomotor symptoms and psychic symptoms can be treated with estrogen, while irregular bleeding is best treated with combined estrogen and progestagen treatments. Symptoms of lack of estrogen, such as vulvitis, vaginitis, changes in blood lipids, etc., can be treated with estrogens, while osteoporosis is best treated with ethinyl estradiol. Hepatic illness, porphyria, deep venal thrombosis, cerebrovascular illness, and estrogen-sensitive cancer are contraindications to estrogen therapy. Women receiving estrogen treatment live longer by about 4 years, according to some studies, and have a lower average cancer rate than those who do not take estrogen therapy. Estrogen treatment should only be given after a complete gynecologic examination with periodic cytologic and blood pressure check-ups.^ieng

Treatment of climacteric and postmenopausal women with 17-beta-oestradiol and norethisterone acetate.

PIP: 3 preparations of 17beta-estradiol and norethisterone acetate were administered to 34 climacteric and 175 postmenopausal women to treat climacteric symptoms and symptoms of estrogen deficiency. 56 women were treated with trisekvens (Group 1), 131 with trisekvens forte (Group 2), and 22 with estrofem forte (Group 3). Triglycerides, cholesterol, calcium, sodium and potassium ions, alkaline phosphatase, creatinine, glucose, protein, albumin, haptoglobin, zinc sulphate, iron, TIBC, bilirubin, ALAT and ASAT, and follicle stimulating hormone (FSH), luteinizing hormone (LH), and low polar estrogens (LPE) were measured. All patients exhibited lowered S-cholesterols which reverted to normal after 6 months treatment. S-triglycerides were unchanged except in Group 1 patients where there was a slight increase after 24 months use (p .01). Serum FSH and LH decreased during treatment and this decrease was most pronounced in Groups 2 and 3. Serum LPE levels increased in Group 1, for climacteric women, to normal luteal values and in postmenopausal women to proliferation values. In groups 2 and 3, serum LPG for postmenopausal women reached luteal values. Climacteric symptoms disappeared with therapy and there was an improvement in symptoms caused by estrogen deficiency. 34 patients discontinued treatment, 14 changing to another preparation. These preparations were well tolerated with few side effects.^ieng

Basic levels of the immuno suppressive serum protein PZ in women-influence of age, parity, gonadotrophins and estrogens.

The basic levels of the pregnancy zone protein (PZ) were measured by a radio-immunoassay, in 270 women of various age. All women were apparently healthy taking no drugs. Values were correlated to age, parity, gonadotrophins and estrogens. A significant age dependent increase was found for PZ while no influence could be attributed to the other factors studied. The present results emphasize that the age dependent variation of PZ concentration should be considered when clinical data of this protein are evaluated.

Influence of aging upon the urinary hormone excretion in the male.

The urinary excretion of LH, low polar oestrogens, neutral C19 and C21 steroids was measured in normal healthy males aged 20-79 years. No significant changes could be noted for the excretion of LH, pregnanediol and 17-ketogenic steroids between 50 and 79 years. The excretion of androsterone and aeticholanolone was significantly lower in the oldest group (70-79 years). A significant drop in the excretion of DHA was noted at approx. 60 years. The excretion of low polar oestrogens remained constant from 20 to 55-59 years, but showed a highly significant (P less than 0.001) decrease at about 60 years. This drop might reflect a sudden decrease in the plasma levels of oestrone sulphate due to a decreased sulphurylating activity in the liver.