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Objective: Our purpose was to compare the effects of a new estradiol-releasing vaginal ring with progesterone given as a vaginal suppository, versus the efficacy, safety and acceptability of an intrauterine device releasing levonorgestrel combined with estradiol, delivered transdermally from a patch. Climacteric symptoms, bleeding pattern and endometrial histologic features were studied., Methods: Fifty six parous, postmenopausal women with urogenital symptoms were allocated in two groups for one year: 28 women receiving estradiol by a vaginal ring and a 100 mg vaginal progesterone suppository 7 days every month and 28 women receiving a continuous transdermal daily dose of 50 micrograms of estradiol with a levonorgestrel-releasing intrauterine device inserted. All the patients were subjected to vaginosonographic examination followed by thorough pathological examination of the uterine curetting samples., Results: A mean endometrial thickness (double layer) of 2.9 and 3.0 mm, respectively, was found to be predictive of normal endometrium. Both treatment regiments effectively relieved climacteric symptoms. Endometrial proliferation was not observed. Spotting was more common in the intrauterine device group than in the vaginal ring group., Conclusions: Treatment of urogenital symptoms in postmenopausal women with these two forms of hormone replacement therapy is shown to be an effective and safe method, exhibiting advantages over other methods of treatment.

Purpose: To determine the effect of progestin therapy on bone mineral density in postmenopausal women and to compare its effects to those of estrogen., Subjects and Methods: A prospective, randomized clinical trial was performed in 81 postmenopausal women aged 51.7 +/- 4.4 years (mean +/- SD). They were assigned to one of four groups: Provera 20 mg, Premarin 0.6 mg, Premarin 0.3 mg plus Provera 10 mg, and a placebo. In addition, all women received calcium supplementation, if necessary, to a calcium intake of 1,000 mg/day. We used single- and dual-photon absorpiometry, metacarpal radiogrammetry, and computed axial tomography to measure bone mineral density in the total skeleton, spine, radius, and metacarpal., Results: Women receiving placebo lost bone at all sites (p less than 0.01). The Provera-treated group showed no change in total body calcium, but there were decreases in radial density (p less than 0.01), metacarpal cortex (p less than 0.01), and spine density (p less than 0.01). The Premarin-treated group had an increase in spine density and total body density (p less than 0.05), but a decrease in radial density (p less than 0.05). The Premarin-plus-Provera group showed no change in spine density, total body calcium, or radial density but had a decrease in metacarpal cortex (p less than 0.01)., Conclusions: Compared to placebo, Provera reduced the rate of loss in cortical areas of the skeleton, but not in the spine, which contains more trabecular bone. In contrast, Premarin reduced the rate of loss in both cortical and trabecular areas of the skeleton. The low-dose combination of Premarin plus Provera was similar in its effect on bone to that of Premarin alone, suggesting that there may be a synergistic effect of this hormone combination on bone. Serum cholesterol levels decreased with Provera, Premarin, and the combination of both, whereas levels of serum triglycerides increased with Premarin treatment, decreased with the Provera regimen, and were unchanged with the combination therapy. Provera does not adversely affect the lipid profile.

Twelve endometrial cancers have been observed before and during progestogen treatment. Eight were well-differentiated and displayed an objective response. It was essentially characterized by a volumetric reduction of the nucleus and the disappearance of tetraploid nuclei. The DNA content remained diploid or near-diploid. Reduction of nuclear non DNA proteins under hormonal treatment is suggested.

Interactions between the estradiolreceptor and the progesteronereceptor are known to exist in the uterus. The "priming effect" of estradiol is likely to exist also in human and rat mammary tumors. In detecting also the progesteronereceptors along with the estrogenreceptors, one cannot only demonstrate the presence but also the activity of the estrogenreceptor. This finding should improve the response rate of hormonesensitivity to receptorpositivity. However preoperative irradiation possibly induces negative progesteronereceptortiters in human breast tumors.

Recurrent gastrointestinal bleeding ceased after the institution of estrogen-progesterone therapy in a patient with gastrointestinal angiodysplasia without chronic renal failure. The patient did have aortic stenosis and mitral insufficiency murmurs. A therapeutic trial of conjugated estrogen should be considered in patients with recurrent gastrointestinal bleeding secondary to gastrointestinal angiodysplasia after the use of therapeutic endoscopy and/or surgery.

Ovariectomy increases the percentage of total lipids in liver, kidney and uterus of intact cyclic rats. Estrogen and progesterone, when administered individually to ovariectomized rats, caused a decrease in the total lipid content of all tissues. Th effect of progesterone in estrogen-primed rats is not significant. Triglyceride and cholesterol content increases after ovariectomy; treatment with estrogen in ovariectomized rats led to a decrease in the concentration of these lipids. Progesterone has no significant effect on these lipids but showed an antagonistic action when given in estrogen-primed ovariectomized rats. The proportions of ethanolamine, choline and inositol phospholipids decreased after spaying and increased when estrogen was given to spayed rats. Progesterone alone had effect only on the uterus whereas progesterone administered to estrogen-primed rats showed an antagonistic effect in all tissues.

Oestrogen and progestin receptors are present in the cytosol and nuclear compartments of normal human endometrium, partly associated with their endogenous ligand hormones. Receptor concentrations fluctuate in relation to the menstrual cycle. Hyperplastic endometrium tends to contain high concentrations of cytosol progestin receptor, whereas the levels of cytosol and nuclear progestin receptors in endometrial adenocarcinoma are lower than in non-neoplastic endometrium. The receptor levels seem to decline with decreasing differentiation of the tumour. Progestin treatment extending over several weeks decreases cellular oestrogen and progestin receptor content in both hyperplastic and malignant endometria. Information based on small patient series suggests that patients suffering from advanced or recurrent endometrial carcinoma and having significant concentrations of both receptors in the tumour tend to have a more indolent clinical course than patients with absent or low tumour receptors. Patients whose lesions are progestin receptor-rich more frequently respond to progestin administration than those with receptor-poor tumours. In contrast, patients with advanced or recurrent disease after progestin treatment and with low tumour oestrogen and progestin receptor concentrations respond more often to combination cytotoxic chemotherapy than patients with higher tumour receptor levels. More data are needed about the clinical correlates of receptor determinations in human endometrial carcinoma to confirm these encouraging preliminary results, before the clinical significance of the determinations can be settled. since there are marked differences in the receptor concentrations reported by various investigators, possibly for methodological reasons, comparison of receptor data and treatment results from different groups is sometimes very difficult.

Results froma prospective study in Malmö performed in 1963-65 are used to discuss the possible role of hormonal drugs in human fetal maldevelopment. Appr. 2 per cent of all women had a child born were treated with gestagens during early pregnancy and slightly more had used Primodos as a pregnancy test. No harmful effect on embryonic development can be demonstrated.

Twenty women with physiological (11) or post-operative (9) lack of oestrogen and progesterone developed progressively painful decalcifying osteosis. Improvement was obtained (after eliminating all contra-indications) by treatment with an oestrogen (17-bêta oestradiol-14 times) associated with a progesterone (14 times ) and increased calcium and phosphates (11 times). Clinical improvement was still present after a period varying from 6 to 36 months, with disappearance of the pain symptoms in 7 cases, and very great improvement in 9 cases. After 6 months of treatment there was also a significant reduction in the biological signs of bone resorption (blood phosphorus levels, calcium-creatinine ratio in morning urine specimens taken after fasting, total calcium in a 24-hour urine specimen). The improvement noted, both clinically and biologically, confirms the effect of oestrogens in reducing bone resorption, underlines their preventive and also curative action, and makes them suitable for use in decalcifying osteosis due to hormone lack, after eliminating all contra-indications and under strict regular supervision (breasts and endometrium).

Tumours and proliferates of the testes from spermatogenic epithelium were treated with estrogens, and those from the interstitial cells-with androgens and 17-hydrosyprogesterone caproate. Depression of the folliculo-stimulating function of the pituitary body with a simultaneous stimulation of the luteinizing hormones (LH) production under the effect of estrogen led to cessation of teratoma and seminoma growth, and to the resolution of the proliferates. When androgens or 17-hydroxyprogesterone caproate were used, depression of the LH led to cessation of the tumour growth, and to the resolution of proliferion of proliferates from the interstitial cells.

Captive squirrel monkeys show a seasonal response to a subtle ovulation induction regime of the five days of progesterone, four days FSH (1 mg/day) and a dose of HCG (500 IU), with the minimal response occurring from July to September. A 3 times 3 factorial design with 18 adult female monkeys was used to determine the effects of increasing doses of HCG (500, 1,000, OR 1,500 IU) and increasing dose of duration of FSH (1 mg for four days, 2 mg for four days, or 1 mg for five days) on ovulation between early July and mid-October. An increase in either dose or duration of FSH increased ovulation while increasing HCG was ineffective.

The in vitro interference of some gestagens with the binding of 3H-17-beta-oestradiol to cytosol specific receptors was investigated with a view to elucidating the mechanism of action of progestins in the treatment of human hormone-dependent breast cancer. A decrease (up to 85%) of oestradiol binding capacity was observed with high concentrations of progesterone, clogestone and medrogestone. These findings are in good agreement with those previously obtained by the same progestins in our laboratory on rat uterine estrogen receptors in vitro or in vivo. These results provide the support for the hypothesis that the mode of action of progestins in the therapy of mammary and perhaps uterine carcinomas is to some extent related to the inhibition of oestradiol binding to cytosol specific receptors.