Platelet serotonin content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms.

Platelet serotonin content was measured by high pressure liquid chromatography in 56 peri- and postmenopausal women, in order to study variations of this parameter with hormonal status and depressive mood symptoms. Clinical symptoms were assessed by a self-report depression symptom scale (CES-D of NIMH). Thirty-eight women with a score of 16 or more were considered as presenting depressive symptoms (mean score +/- SD = 28.8 +/- 10.5), while the others formed the control group (n = 18, score = 4.4 +/- 4.2). Platelet serotonin contents were significantly lower in the 'depressed' group (0.302 +/- 0.010 vs. 0.366 +/- 0.020 nmol 10(-8) platelets, means + SEM, P less than 0.001 by Mann-Whitney U-test). In 'depressed' women who had been treated for one or more depressive episodes, platelet 5-HT contents (0.283 +/- 0.023, n = 18, P less than 0.01) were significantly lower with respect to controls. In patients without previous episodes of depression, serotonin expressed in nmol 10(-8) platelets did not differ significantly from controls but serotonin expressed in nmol ml-1 of blood was slightly lower than control values (0.890 +/- 0.085, n = 20 vs. 1.088 +/- 0.090 nmol ml-1, n = 18, P less than 0.02). Platelet serotonin content was positively correlated to plasma oestrone and oestradiol concentrations among the control group but not in the 'depressed' group.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrium and plasma hormone profile in the peri-menopause and post-menopause.

Endometrial histology and plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-oestradiol (E2), oestrone (E1) and progesterone (P) were studied in 483 women over a period of 13 yr (6 yr before and 7 yr after the start of definitive amenorrhoea, defined as the last menstrual bleeding). The patterns for these parameters were established on the basis of the results of 1227 gonadotrophin and steroid determinations and 721 endometrial biopsies. Three periods were identified. During the first, from year-6 to year-3, gonadotrophin levels increased gradually, while those of E2 remained normal, with peaks in some cases. Mean plasma P levels were within the normal range until year-3, but they then decreased progressively. Endometrial histology was similar to that observed during reproductive life. In the second period, from year-3 to year+1, there was a concomitant rise in gonadotrophins as the E2 and P levels decreased. However, at the start of definitive amenorrhoea, the mean E2 and P levels fluctuated between 60 and 100 pg/ml and between 2 and 3 ng/ml, respectively. The endometrium reflected this decrease in E2 and P production. It was not atrophic but proliferative when definitive amenorrhoea commenced. During the last period, from year+1 to year+7, gonadotrophins reached a plateau at high levels, while those of E2 continued to fall, reaching very low values at year+4, after which they reached a plateau. P levels were at the detection limit of the technique. The correlations between all plasma steroid levels and endometrial histology demonstrated discrepancies in 30% of cases: proliferative or hyperplastic endometria were seen at E2 levels of under 60 mg/ml, atrophic endometric at E2 levels of over 60 pg/ml and secretory endometria at very low P levels.

Multicentre study of effects of Org OD 14 on endometrium, vaginal cytology and cervical mucus in post-menopausal and oophorectomized women.

A multicentre study covering 69 post-menopausal or oophorectomized women was performed to determine whether Org OD 14 [7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) administered orally in a daily dose of 2.5 mg for 90 consecutive days induces endometrial proliferation. The treatment with Org OD 14 was continued in combination with 1 mg/day of lynestrenol from day 91 for 10 days to ascertain whether secretory transformation of the endometrium and subsequent withdrawal bleeding would occur. Endometrial biopsies were obtained before treatment and on day 91. The effects of Org OD 14 on vaginal mucosa and cervical mucus were also evaluated. Org OD 14 did not display any effect on the endometrium in 56 of the study subjects (83.5%). Weak stimulation (initial proliferation) was seen in 11 of the subjects (16.4%) and withdrawal bleeding occurred in only 5 of these after cessation of the combined treatment with lynestrenol. However, moderate 'oestrogenic' effects on vaginal mucosa and cervical mucus were induced in all study subjects.

[Preservation of the ovaries in peri-menopause]. / Conservation des ovaires dans la péri-ménopause.

The authors analyse the motivation for allowing conservation of healthy ovaries when surgical operations are being undertaken round about the time of the menopause. When patients who are at risk are excluded, and when pathological ovaries are excluded, as also when there is a technical impossibility of conserving the ovaries, they can be conserved. This implies that one should check the ovary that is left behind histologically, especially looking for the risk of cancer developing later. Although this is slight it nevertheless has to be emphasised. The authors further their argument by reference to the anatomical, physiological and hormonal state of the ovary around the time of the menopause. Although the hormonal state changes and is less intense with a relative increase in the secretion of D4 androstenedione and sometimes even of oestradiol, the ovary does remain an organ that secretes actively around the time of the menopause and even past the confirmed menopausal state. The inclination to conserve ovaries should not be a systematic one but every case should be considered on its own merits.

Efficacy and safety of Org OD 14 in the treatment of climacteric complaints.

To study the effect of Org OD 14 [17 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) on the endometrium, 9 healthy post-menopausal women were given a daily dose of 2.5 mg of Org OD 14 for 100 consecutive days. In addition, during days 91-100 a daily oral dose of 1 mg of lynestrenol was taken by each volunteer. Endometrial biopsies were obtained before the start of treatment and on day 91. At pre-treatment, the endometrium was atrophic in 7 out of 9 volunteers and weakly stimulated in 2 volunteers. On day 91, the endometrium was found atrophic in 8 out of 9 volunteers and weakly stimulated in 1. Breakthrough bleeding occurred in 1 volunteer. After cessation of the combined treatment with Org OD 14 and lynestrenol, withdrawal bleeding occurred only in 1 volunteer. To assess the efficacy of Org OD 14 in the treatment of climacteric complaints a double-blind cross-over study was performed in 29 post-menopausal women. Patients were randomly allocated to Org OD 14 or to placebo as first treatment. Each period of treatment lasted 4 mth; no wash-out period was introduced. Patients took 1 Org OD 14 tablet (2.5 mg) or 1 placebo tablet per day. The patients scored hot flushes and sweating. At the end of the second treatment period, each patient was asked which of the 2 treatments she preferred. Data sufficient to allow for a conclusion were obtained from 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovestin vaginal cream and suppositories for the treatment of menopausal vaginal atrophy.

Eighty-two postmenopausal women with vaginal atrophy and associated symptoms were treated with either Ovestin vaginal cream (54 women) or vaginal suppositories (28 women) containing 0.5 mg of E3/dose, daily for 3 weeks. A maintenance dose of 0.5 mg of E3 twice weekly was applied by all patients for 5 weeks, and by 27 of them for up to 16 weeks. Variables studied were clinical and colposcopic findings, the Maturation Index (MI) and Maturation Value (MV), cervical mucus ferning (F) and spinnbarkeit (S) and endometrial biopsies (obtained pretreatment and after 3 weeks in 15 of the patients). Furthermore, the bio-availability of circulating unconjugated E3 for up to 8 hours following a single dose of Ovestin cream was studied in 10 of the patients. Clinical and colposcopic findings indicated that the treatment had a very favourable effect in all patients. This was reflected in the pronounced change in vaginal smears, indicating a strong oestrogenic effect. There was a slight to moderate effect on cervical mucus. Endometrial biopsies showed that endometrium remained atrophic in all 15 patients in whom biopsies were obtained. A maintenance dose of 0.5 mg of E3 twice weekly appeared to be sufficient to maintain the beneficial effect. Tolerance was good, and patients commented favourably on the treatment.

Histological responses of the endometrium to the IUD.

PIP: Histological studies of endometria after IUD use were conducted in 592 women (mean age, 32 years; range, 22 to 48 years). Duration of IUD retention was not considered in these studies. Bacteriological studies were also performed in 108 cases after IUD removal by sterile technique. The following conditions were observed: 1) direct mechanical action of the IUD on the endometrium; 2) hormonal modification; 3) pregnancy modification; 4) vascular modification; and 5) inflammatory modification. The observed conditions suggest that IUD action on the endometrium resembles that of a foreign body inserted into a semiclosed cavity. The IUD is constantly in contact with the uterine cavity, the tubes, and the peritoneum. It appears to enhance various germ infections and this was attributed to increase in number of sexual partners (due to little fear of pregnancy) and less rigorous hygienic care. Hemorrhages in the form of menorrhagias or metrorrhagias were found to be one of the most frequent complications associated with IUD use, and one of the main reasons for termination of IUD use. Although the endometrium contains mucosa which triggers its defense mechanisms by means of lysozomes, the IUD induces mechanical vascular and hormonal reactions which affect endometrial resistance to infection.^ieng

[Histological response of the endometrium to IUD's (author's transl)]. / Responses histologiques de l'endometre aux sterilets.

PIP: The authors performed 592 histological examinations of the endometrium in contact with 5 different types of IUD. 4 parameters were considered, the purely mechanical action of the device causing lesions on the endometrial surface, hormonal modifications, vascular modifications, usually related to menorrhagia and/or metrorrhagia, and inflammatory modifications, which can be related to IUD presence, or caused by external infection. The analysis of the histological parameters of IUD action of the endometrium showed their very complicated interrelation; the endometrium does nto simply react to a foreign body, the IUD, but it is a hormonal-dependent tissue, thus representing a link in a large and complex hormonal- and neurosympathatic system, which is, as yet, not perfectly known.^ieng

[A histological and hormonal study of 399 women near the menopause or with confirmed menopause (author's transl)]. / Etude histo-hormonale de 399 périménopauses et ménopauses confirmées.

This work is concerned with 399 women who were either near the menopause or had had the menopause and on whom 476 hormone levels and 169 examinations of the endometrium had been carried out. It is possible to put the women into three groups. 13 p. 100 showed a diphasic cycle, with more or less normal ovarian function. Among the group of women whose cycle was not diphasic an appreciable number had normal oestrogenic activity, or were indeed hyperoestrogenic. The others were hypo-oestrogenic. Several facts can be derived from this study. Raised levels of E.2 can be found even when there is no cyclical activity and even in women who have raised levels of FSH. Normal ovarian function may be resumed several months after the menopause, although when the levels of FSH are raised the occurrence of the postmenopausal state would seem to be confirmed. The presence of hot flushes does not seem to correspond to a particular hormonal state. Marked differences seem to exist between the levels of the plasma hormones and the endometrial biopsy results. It is possible to have an atrophic endometrium with a raised level of oestradiol-17 beta, or on the other hand a polypoidal endometrium in women who are hypo-oestrogenic. The presence of levels of progesterone such as are found in a normal luteal phase does not indicate that the endometrium will necessarily be secretory. These contradictions cannot be resolved by studying the intra-cellular concentrations of the hormone receptors. The approach of the menopause is not always characterized by a progressive and continuous state of oestrogen deficiency or by hypophysial overactivity. This classical picture can be heavily shaded. All kinds of hormone profiles and responses by the receptor organs may be met and the clinician should be aware of these facts when he chooses therapy.

[Breast cancer diagnosed in the pre-clinical stage with the phenomena of histological regression (author's transl)]. / Cancer du sein dépisté au stade pré-clinique avec phénomènes de régression histologique.

The discovery of carcinomatous cells in a discharge from a breast, without any other clinical, mammographic or thermographic sign, allowed the removal of a carcinoma in its pre-clinical stage. The histological study in a series of cuts showed a carcinoma that was still intraductal and which showed signs of cellular regression accompanied by marked peri-canalicular sclerosis associated with inflammatory infiltration. This observation allows commentaries to be made concerning the immunological process that goes with carcinoma in its intra-epithelial stage and permits the possibility of predicting an advance in the understanding and treatment of carcinomata which should be diagnosed very early.

[A previously unpublished indication for sulpiride: functional uterine hemorrhages]. / Une indication inédite du sulpiride: les hémorragies utérines fonctionnelles.

Sulpiridin has been shown to be remarkably efficient in treating functional uterine haemorrhage (70 per cent success). It is especially so in the pre-menopause. Its mode of action takes place on three levels: the hypothalamus, where it works on the clonic centre for the release of gonadotrophins (the tonic centre not being affected); the ovaries, where it lessens the sensitivity of the reaction of the ovary to gonadotrophins; the uterus, where there is direct action on the thickness of the mucous lining of the uterus and on its blood supply.

[Unsaponifiable fractions of the avocado and soy bean in gyneocology]. / Les insaponifiables de l'avocat soja en gynécologie

The experimental work of Robert on the action of the unsaponifiable fractions of the avocado pear and soya bean on inflammatory granulomata of the rat gives rise to the supposition that these have a selective action on inflamed connective tissue by a process of katabolism of collagen through proteolytic enzymes. We have used this anti-inflammatory and collagenolytic action in gynaecology, with favourable results particularly in post-inflammatory and post-infective conditions as well as scarring in the pelvis. The decongesting action of the unsaponifiables of the avocado pear and the soya bean seems also to have a role to play in cellular tissue reactions in the pelvis after cobalt therapy, and in recent retractile scars and in breast inflammations, as well as to prevent scar reactions after operations. Since treatment has to be for a long time and well tolerated, the blood lipids should be estimated as a safety measure. If this is done the unsaponifiables seem to have a place in the treatment of inflammatory conditions in gynaecology.