F. Bottiglioni

Use of Org OD 14 for the treatment of climacteric complaints

The effects of treating climacteric complaints in post-menopausal women were studied in an open trial in which Org OD 14, a placebo and no treatment were compared. In addition to the symptomatic effects, clinical and laboratory parameters were also studied. One hundred and twenty-four women who had undergone a natural or surgical menopause completed 4 mth of randomized treatment; 35 received Org OD 14 (2.5 mg/day, per os), 46 a placebo, and 43 no treatment. The mean ages and time in years since menopause were comparable for each group. The parameters were assessed before treatment and after 4 mth. The results in the group treated with Org OD 14 were compared statistically with those for the other two groups using the chi 2 test, Students t test or analysis of variance. A beneficial effect on clinical parameters was seen following Org OD 14 treatment. The results as regards hot flushes and sweating were significantly better statistically than those in the other groups. Org OD 14 was found to have no effect on the endometrium, breasts, body weight or blood pressure, while vaginal atrophy was slightly improved. Serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and phosphate were slightly reduced by Org OD 14. Liver function tests, clotting factors and the other routine laboratory parameters were not affected by Org OD 14 treatment. It was concluded that Org OD 14 is an effective and safe compound for the treatment of climacteric syndrome.

Intramuscular interferon-β treatment of cervical intraepithelial neoplasia II associated with human papillomavirus infection

A placebo‐controlled trial to evaluate the efficacy and the safety of intramuscular injection of interferon‐p has been performed on 37 patients suffering from cervical intraepithelial neoplasia II (CIN II) associated with human papillomavirus (HPV) infection of the cervix: twenty‐two patients were treated with interferon‐β (2 × 106 I.U. daily) for ten days; fifteen received placebo (2 ml of saline solution daily) for ten days. Prior to therapy, and at day 70, 190. 370. 550, 730 after the beginning of treatment, patients were examined by colposcopy and punch biopsies of the cervix. Results showed a progressive amelioration in the interferon‐β treated patients. which was statistically significant at any control station (70, 190, 370, 550, 730 days) as compared to placebo treatment. Percentages of lesions that regressed, persisted or progressed were 36.4%, 54.5%, 9.1% respectively in the Interferon‐β group, and 0%, 67.7% and 33.3% respectively in the placebo group. Interferon‐β administered intramuscularly has shown to be an ellicacious treatment of CIN II (cervical intraepithelial neoplasia II) associated with HPV infection, without evident side effects; it can be used in patients requiring medical treatment with at least one‐year monitoring by cervical biopsies or as an adjuvant surgical treatment (which remains the principal treatment) in the management of patients suffering from CIN II associated with HPV infection.

Female sexual activity as a function of climacteric conditions and age

By establishing a statistical profile of the average sexual behaviour of women during the climacteric period, an attempt was made to determine what influence the climacteric had on female sexual activity. With the advancement of age, the sexual activity of women tends to decline. The menopause itself tends to further reduce the retrogression of the sexual activity in women.

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT

Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.

Body mass index distribution in climacteric women.

Body Mass Index (BMI) was calculated in 2481 climacteric women selected from among the outpatients attending the Menopause Clinic at Bologna University in absence of hormonal replacement therapy and diseases that could cause weight gain. Analysis of variance of the W/H2 (weight/height squared) distribution in different age and climacteric situations demonstrates that the pre-menopause is a weight-gain inducing state and that ageing seems to cause a progressive increase in W/H2.

A study of thyroid function in the pre- and post-menopause

Serum levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triidotthyronine (FT3), free thyroxine (FT4) and thyroxine-binding globulin (TBG) were measured in 382 healthy women who were attending a menopause clinic. Of these women, 140 were in the pre-menopausal phase, 162 had been post-menopausal for less than 3 yr and 60 had been post-menopausal for greater than 3 yr. Analysis of the results as a function of climacteric situation, revealed that the only significant difference was a lower serum concentration of FT3 in the women who had been post-menopausal for over 3 yr than in the women who were in the pre-menopausal phase. Statistical analysis of the results as a function of both climacteric situation and age showed that the serum level of TBG increases with age, while serum levels of circulating thyroid hormones decrease, and that although the menopause does not bring about marked changes in thyroid function, it nevertheless tends to reduce that function, especially when menopause occurs at the expected time. Finally, by correlating values with T4 values on an individual basis, it was possible to ascertain that when physiological changes in thyroid function do occur in the climacteric, they are not caused by primary changes in TSH secretion.

Analysis of the climacteric syndrome

The climacteric syndrome (CS) was investigated in a large sample of women (over 4000) who spontaneously attended the Menopause Clinic at the University of Bologna between 1976 and 1986. The participants selected had received no hormonal replacement therapy for at least 6 mth or any other drug for at least 3 mth previously. They were all free from any disease that could influence any of the CS symptoms. The frequency of 12 symptoms considered typical of the CS was investigated. The interrelationships between these symptoms were determined as well as the frequency of the occurrence of individual symptoms in association with various climacteric complaints. The results indicated (a) that the CS is not uniform but both variable and individual, (b) that the frequency of its constituent symptoms remains high in advanced fertile age and the advanced postmenopause, (c) that the symptoms are preferentially interlinked, (d) that many, but not all, symptoms exhibit a differentiated pattern during the course of the natural and surgical menopause/age progression, and (e) that hot flushes and sweating, and to some extent insomnia and headache, are menopause-dependent.

Dihydroergocristine in stopping lactation: Double-blind study vs bromocriptine

In a double-blind study vs bromocriptine, 30 women who wished to interrupt breast-feeding after a physiological delivery and at least 3 months of nursing were given at random 10 mg dihydroergocristine capsules or 2.5 mg bromocriptine capsules twice a day for 5 days, then 3 times a day for 5 days if treatment had failed to produce an effect. The parameters considered were PRL plasma levels, which were measured at baseline, on the 5th day and, where necessary, on the 10th day of treatment. Milk secretion, breast swelling and pain were recorded at baseline and daily during treatment. The appearance of any side-effect was accurately reported. A prolactin decrease was observed in both groups (p less than 0.01). After 5 days milk secretion was reduced more significantly in the dihydroergocristine group; after 10 days of treatment 6 cases treated with bromocriptine and 1 case treated with dihydroergocristine still revealed a low milk secretion. Breast congestion and pain were absent in both groups. As regards side-effects, a significant decrease in systolic blood pressure (standing position) was reported in the bromocriptine group. Other symptoms, such as nausea, vomiting, insomnia and headache, were reported in 8 patients in the bromocriptine group vs 6 patients in the dihydroergocristine group.

Premenopause-Dependent Changes

The authors retrospectively evaluated 1,773 climacteric outpatients in order to establish: (a) criteria able to distinguish different conditions in the transitional phase before menopause (advanced fertile age and premenopause) and (b) premenopause-related changes during the transition from one to the other of several clinical and laboratory parameters. Results showed an increase in gonadotropin plasma levels, a decrease in estrogen plasma levels and a greater frequency of women complaining of hot flushes in premenopause compared to advanced fertile age, as an expression of the progressive decline of ovarian function. Premenopause-related changes were a decrease in thyroid function and an increase in the body mass index, the beginning of bone loss, an increase in glucose, total cholesterol and triglyceride serum levels and a greater frequency of women complaining of hypertension and urinary stress incontinence. An increase in total proteins, uric acid and aminotransferase serum levels was also noted.

Physiopathological aspects of body overweight in the female climacteric

The correlation between overweight and the climacteric was studied in 550 menopause clinic patients by investigating certain clinical and sociocultural parameters (age, marital status, educational level, occupation and type of work, calorie intake, smoking habits, parity, blood pressure, previous hormonal therapy and climacteric symptoms), evaluating plasma levels of various hormones (17 beta-oestradiol, follicle-stimulating hormone (FSH), luteinizing (LH), testosterone, hydrocortisone, adrenocorticotrophic hormone (ACTH), triiodothyronine (T3), thyroxine (T4), growth hormone (GH) and insulin), glucose and various lipid fractions (total lipids, total cholesterol, nonesterified fatty acids (NEFA), triglycerides and phospholipids) and exploring the blood-clotting pattern ( Owren s test, euglobulin lysis time, antithrombin III and prothrombin agglutination time (PAT). The subjects were classified as normal weight or overweight by reference to Brocas Index, as modified by Brusch , and the degree of overweight was determined by means of the Body Mass Index (BMI). Of the subjects examined, 49% were overweight and, in successive years following the menopause, there was a growing bipolarization of the weight increase. The correlation between overweight in the climacteric and the parameters considered was found to be significant only in regard to calorie intake, age and educational level. Post-menopausal gonadotrophin levels in blood were significantly lower in the overweight than in the normal-weight women. With the onset of menopause, the plasma level of testosterone fell in the normal-weight women, while it increased, along with that of hydrocortisone, in the overweight women. In the normal-weight women at menopause, it was found that there was a tendency towards a substantial increase in lipid fractions and glycaemia, as well as a state of hypercoagulability. In the overweight women, the tendency was towards an even more marked increase in both glycaemia and the various lipid fractions, and, besides the hypercoagulative state, there was an associated reduction in fibrinolytic activity. It is concluded that the menopause not only causes metabolic changes but also aggravates the metabolic and endocrine tendencies which characterize overweight subjects and thus, clinically, constitutes an obesity risk factor in those women who already demonstrate a tendency towards overweight in the pre-menopausal phase.