Beta-interferon treatment of cervical intraepithelial neoplasia: a multicenter clinical trial.

Forty-nine women with cervical intraepithelial neoplasia (CIN) grade II were treated with systemic and/or local beta-interferon (beta-IFN) applications. The aim of the study was to compare the efficacy of different routes for the administration of beta-IFN, evaluate local and systemic beta-IFN tolerance, and determine whether disappearance of neoplastic lesions was related to the resolution of the concomitant human papillomavirus infection. The patients were randomized to receive intramuscular, intralesional or a combination of intramuscular and intralesional administration, or conventional treatment. Significant differences in the rate of lesion regression were observed between treated and untreated women. The highest frequency of complete response was observed with the therapy combining intramuscular and intralesional treatment.

Uterine fibroids: protocols of integrated medical/surgical treatment.

Uterine fibroids are the most common solid pelvic tumor in women and in these last years their management has been deeply reviewed. An optimal integration of GnRH analogue treatment with different surgical techniques require an adequate work-up for the specific problems of each single patient. For a correct management of these patients, we divided them into 4 categories on the basis of symptoms and specific objectives to persuasive: a) perimenopausal patients; b) young patients, symptomatic or with large myomas, with no wish for more children; c) young patients, symptomatic or with large myomas, wishing to preserve fertility; d) infertile patients or patients with history of repeated miscarriages. Our suggested work-up is the following: a careful USGraphic evaluation of fibroid size and localization, a transvaginal doppler examination of the uterine blood supply, a complete haematochemical analysis, a hysteroscopy guided biopsy and a complete bone evaluation. On the basis of the above mentioned evaluations for each group we will use a different therapeutic approach in regard of either length of medical treatment (for tree to six months, for one or more cycles) or necessity of surgical treatment (with the possibility to get a natural menopausal), or different surgical techniques (operative hysteroscopy and/or laparoscopy, laparotomic myomectomy, vaginal or abdominal hysterectomy.

Double-blind controlled trial of progesterone vaginal cream treatment for cyclical mastodynia in women with benign breast disease.

The clinical effectiveness and safety of vaginal micronized progesterone treatment in mastodynia were evaluated in a double-blind placebo controlled study. Eighty regularly menstruating women affected by severe cyclical mastodynia were randomly assigned to two groups of 40 patients. One group was treated for 6 cycles from the 19th to the 25th day of the cycle with 4 g of vaginal cream containing 2.5% natural progesterone. The other group was similarly treated with placebo. The treatment was preceded by a control cycle. All patients reported every day their breast pain on a 100 mm visual linear analogue scale (VAS). The response of breast tenderness and nodularity to treatment was assessed by clinical examination. Vaginal progesterone resulted significantly more efficacious than placebo in reducing mean ratings of breast pain on VAS and mean scores of breast tenderness to touch. Success of treatment, defined as reduction greater than 50% of basal mean score of breast pain on VAS, was achieved in the 64.9% of patients treated with progesterone and in the 22.2% of patients receiving placebo (p < 0.01). Conversely, at the end of treatment, the improvement in breast nodularity showed a not statistically significant difference between the two groups. No major side-effects were detected.

Leuprorelin acetate depot vs danazol in the treatment of endometriosis: results of an open multicentre trial.

A national multicentre trial was organized in order to compare the efficacy and safety of leuprorelin acetate depot and danazol in the treatment of endometriosis. Sixty-seven patients with pelvic endometriosis of different severity at laparoscopy were included in the study and followed during the 24 weeks of treatment. Leuprorelin acetate depot 3.75 mg was injected every 24 days, while the daily dose of danazol was 600-800 mg. At the end of the study objective improvements induced by the two drugs were observed by a second laparoscopic examination. In addition, at regular intervals during the study semiquantitative evaluation of subjective symptoms were monitored. Scoring the final objective changes in the two patient groups revealed no significant difference, however the women treated with leuprorelin acetate depot registered significantly better control of pelvic pain. Due to its efficacy, tolerability and ease of use, leuprorelin acetate appears to be an excellent drug for the treatment of endometriosis.

The effect of various drugs with neuroendocrine activity and transdermal estradiol on plasma gonadotropin concentrations after ovariectomy in reproductive-aged women.

In the present study we compared the effect of different neuroactive drugs with that of estrogen treatment on the ovariectomy-induced plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) changes. A total of 35 menstruating women undergoing ovariectomy were randomly divided into five groups of 7 patients each, receiving a 4-week treatment with oral clonidine, lisuride and sodium valproate, transdermal 17 beta-estradiol, or placebo. The treatment started the day after ovariectomy. Surgery was done during the early follicular phase of the cycle. Blood samples were collected before and after 3, 5, 7, 14, 21 and 28 days of treatment. During the treatment, hot flushes were subjectively recorded. The placebo-treated group showed a progressive increase in plasma LH and FSH concentration during the month following ovariectomy. The same changes occurred in the lisuride and sodium valproate treated groups. Plasma LH levels in ovariectomized women treated with clonidine showed an increase which was higher than in placebo-treated women (p less than 0.01), while FSH levels were similar to those in the placebo group. In the estradiol-treated group the increase in both gonadotropins was significantly less (p less than 0.01) than in the placebo group. The frequency and intensity of hot flushes were high in placebo and sodium valproate treated subjects, being significantly reduced by clonidine, lisuride and estrogen treatment. Our results seem to indicate that clonidine treatment modulates the LH postcastration rise and that both neuroendocrine and gonadal mechanisms influence the changes in the activity of the GnRH-pituitary axis following ovariectomy.

[Carcinoembryonic antigen in genital infections caused by HPV]. / Antigène carcino-embryonnaire dans les infections génitales à HPV.

The immunohistochemical search for the carcino-embryonic antigen (CEA) was positive in 28.14 per cent of the cases of plane cervical condylomata, in 25 per cent of the cases of infections of the vulva by HPV, and in up to 40 per cent of the cases of cervical or vulvar lesions. These data are in accordance with those reported in the literature, even if the number of cases studied is too limited to enable us to make a significant comparison. As a result, the CEA might prove to be a useful marker for a more accurate biological and chemical classification of genital lesions by HPV.

[Topical treatment with estriol in postmenopausal atrophic vaginitis]. / Traitement topique avec estriole de la vaginite atrophique post-ménopause.

The vaginal application of estriol leads to plasma free estriol levels validated on the basis of laboratory and clinical parameters at a dose very much less than that.

Relationship between cerebrospinal fluid beta-endorphin and plasma pituitary-gonadal hormone levels in women.

Brain beta-endorphin (beta-EP) plays an important role in regulating the hypothalamus-pituitary-gonadal axis activity. Cerebrospinal fluid (CSF) beta-EP levels seem to reflect the central rather than pituitary secretion. With the aim to correlate the changes of plasma estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone with brain beta-EP, CSF levels of beta-EP were measured in 15 normally cycling and 15 postmenopausal women. CSF beta-EP levels in post-menopausal women were lower than in fertile women. A positive correlation between plasma E2 and CSF beta-EP level was found in all women. In fertile women CSF beta-EP levels were inversely correlated to plasma gonadotropin levels. These results showed that CSF beta-EP levels differ between fertile and postmenopausal women and are correlated with plasma LH and E2, suggesting a strong linkage between central beta-EP levels and pituitary-gonadal axis hormones.

[Determination of squamous cell carcinoma antigen in the blood of patients with cancer of the uterine cervix]. / Dossaggio dell'antigene "Carcinoma squamocellulare" (SCC) nel siero di pazienti affette da cancro del collo dell'utero.

The RIA method has been used to assay the squamous cell carcinoma antigen in the serum of twenty-four patients suffering from cervical cancer. The results obtained showed expressive differences between the levels in women with metastatic relapse and in those in remission, but the SCC antigen is particularly useful in the therapeutic monitoring, since it can assess of the current treatment.

[Correlation of carcinoembryonic antigen (CEA) and serum and tissue alpha-fetoprotein (AFP) in malignant tumors of the female genital tract]. / Correlazioni tra antigene carcinoembrionario (CEA) ed alfa-fetoproteina (AFP) sierico e tissutale nei tumori maligni della sfera genitale femminile.

The Authors have carried out determinations of AFP in the serum and of CEA in serum and in surgically removed tissue of 67 patients with genital tract's malignant tumors. As the results obtained among values of pre and post operatory CEA and tissue concentrations are incongruous, they believe useful, within the monitoring of patients with gynecological cancer, dosing CEA in the serum and also on the surgical section trying to reduce so the minimum positive false and negative false. Finally the repeated dosage of these antigens allows to follow the local replaced or the metastasis after some month, before the symptoms are clear.

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovarian disease.

Several reports have shown elevated circulating beta-endorphin (beta-EP) levels in patients with polycystic ovarian disease (PCOD). However, it is not yet clear whether these high beta-EP levels are linked to the etiopathogenesis of PCOD or are secondary to the obesity. In the present study we measured beta-EP plasma concentrations in 19 PCOD patients, 10 with normal weight (Group A) and 9 with excessive weight (Group B), and in 18 normally ovulating women, 10 with normal weight (Group C) and 9 with excessive weight (Group D). beta-EP values were similar in the two groups of non-obese patients and controls. beta-EP concentrations were also similar in the two groups of obese patients and controls, and they were significantly higher (p less than 0.05) than in non-obese patients. Our data indicate that in PCOD, elevated beta-EP values are related to obesity, suggesting that they are not linked to the pathogenesis of PCOD.

The adjuvant treatment of ovarian cancer: result of the pilot study of a new combination chemotherapeutic regimen (DAC).

Twenty-three previously untreated ovarian cancer patients were treated, from January 1986 to March 1987, with combination chemotherapy consisting of cisplatin, cyclophosphamide and cytarabine (DAC regimen). All patients had advanced disease, which included 18 stage III and 5 stage IV patients. Sixteen patients had serous, 6 undifferentiated and 1 mixed histotype. Surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and appendicectomy was performed in only 11/23 patients. Seventeen patients had bulky disease when the treatment was started. Four courses of chemotherapy were initially administered to all patients; second look laparotomy was performed in patients with no clinically measurable disease or with presumable entirely resectable tumor. Vomiting was the major side effect of chemotherapy: myelotoxicity was mild and in only one patient permanent renal damage occurred. A total of 14 objective clinical responses (73.7%) were observed, of which 9 were complete (47.4%). Six clinical complete remissions (37.5%) occurred in the group of patients with bulky disease. At second-look laparotomy six patients were found disease free (26%), 4 of whom originally had bulky disease (25%). Short-term DAC regimen seems to be a very effective treatment, with acceptable toxicity, in patients with ovarian cancer.

Vulvo-vaginal condylomatosis and relapse: combined treatment with electrocauterization and beta-interferon.

The therapeutical effectiveness of beta-interferon and the possibility of reducing the incidence of relapses were evaluated by selecting three groups of patients affected with three forms of condylomatosis and submitting then to various treatments. In the first group of sixty patients treated with beta-interferon, we obtained the best results in micro-condylomatosis (a 100% response), while florid condylomatosis responded less well to the treatment (72% with no response). In the second group of ten patients, electrocoagulation of florid condylomata determined a complete response (CR) in seven cases (70%). Moreover, immunoperoxidase identified three case of sub-clinical infection, two of which relapsed. In the third group of ten patients, we combined electrocoagulation with beta-interferon. This combination showed the effectiveness of beta-interferon in decreasing relapses. This result is evident if we consider that only one out of four patients with immunoperoxidase-positive biopsy relapsed.

Vaginal administration of gemeprost for preoperative cervical dilatation in non pregnant patients.

The use of Gemeprost vaginal suppositories has been evaluated in a trial for induction of the cervical dilatation in non pregnant women. 30 voluntary patients, 22 nulliparous and 8 pluriparous, had to be subjected to biopsy of the endometrium; 24 were treated for the control of sterility and 6 for menstrual perimenopausal disorders. The biopsies of the sterility control were effected in the second half of the cycle, generally without having recourse to narcosis. A single Gemeprost pessary containing 1 mg of 16, 16-dimethyl-trans-delta 2 PGE1 methyl ester was intravaginal administered, deeply into the posterior fornix, 3 hours before the biopsy. The success rate was 86.66 (26 pts.) with an average dilatation of 5.38 H (Hegar) +/- 0.75 SD. For 4 patients (13.33%) having a dilatation less than 4 H, it was necessary to complete the dilatation mechanically. All the observed side effects presented a modest intensity: cephalalgia 6.6% (no. 2), gastralgia 3.3% (no. 1), vaginal burning 6.6% (no. 2). No significant variation of vital function parameters was recorded. In conclusion this type of preparation of the cervix has permitted us to achieve a more gradual dilatation and to prevent the traumata of the cervico-isthmic system due to forced mechanical dilatations by the exclusive use of Hegar's dilators.

Impairment of dopaminergic and opioidergic activity in patients with polycystic ovarian disease is restored by treatment for the induction of ovulation.

The luteinizing hormone (LH) response to metoclopramide (MCP), a dopamine receptor antagonist, and naloxone (NAL), an opioid receptor antagonist, was evaluated in 7 patients with polycystic ovarian disease (PCOD) before and during treatment with purified human urinary follicle-stimulating hormone (hFSH), and in 6 control women during spontaneously ovulating cycles. Before treatment, in all patients both MCP and NAL administration did not increase plasma LH levels. In the 6 subjects ovulating following hFSH treatment the LH response to MCP and NAL at preovulatory and midluteal phases was restored, as it occurred in control women. Our results suggest that in PCOD the dopamine and opioid activity in the hypothalamus are decreased. The reversal of peripheral ovarian response induced by treatment for the induction of ovulation may restore these impaired neuroendocrine activities.

Screening for endometrial adenocarcinoma.

A careful evaluation of endometrial adenocarcinoma risk factors has allowed the AA. to suggest an integrated screening program, including cytology, hysteroscopy and guided biopsy. First results of this program are then described.

Effect of a combination of ethinylestradiol and desogestrel in adolescents with oligomenorrhea and ovarian hyperandrogenism.

Nine oligomenorrheic adolescent girls with a clinical and hormonal picture of ovarian hyperandrogenism were treated with a monophasic oral contraceptive (OC) containing 0.03 mg ethinylestradiol (EE) plus 0.150 mg desogestrel (DOG) for six months. The same treatment was administered in eight eumenorrheic adolescents. In both groups the treatment induced a decrease in LH, FSH, androstenedione (delta 4-A), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) levels associated with a significant sex-hormone-binding globulin (SHBG) increase. In oligomenorrheic adolescents a marked decrease in both the total ovarian volume and the number of cystic follicles was observed. All parameters, except SHBG and ovarian volume in hyperandrogenic girls, returned to pre-treatment values 3 months after treatment. Subjective improvement of skin problems occurred in six of the nine oligomenorrheic girls. Although temporary, the EE + DOG formulation pill is effective in the treatment of ovarian hyperandrogenism in adolescents. It may also be useful for the prevention of the progressive transformation in the 'classical' and 'irreversible' micropolycystic ovary of adult age.

PIP: The hormonal effects of a combined, monophasic oral contraceptive (OC) containing 0.03 mg of ethinyl estradiol and 0.150 mg of desogestrel were compared in 9 adolescents with oligomenorrhea and ovarian hyperandrogenism and 8 controls with regular menstrual periods. All adolescents were treated for 6 consecutive months. Before treatment, the females with irregular periods had significantly higher basal luteinizing hormone (LH), delta 4-androstenedione (A), testosterone (T), and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. In addition, the oligomenorrheic females had significantly lower sex hormone binding globulin (SHBG) levels and greater mean ovarian volume. OC treatment produced a decrease in all hormones (LH, follicle-stimulating hormone, delta-4 A, T, and DHEA-S) in girls in both groups and a significant increase in SHBG levels. Oligomenorrheic subjects further manifested a significant decrease in total ovarian volume, with reduced number or disappearance of all echo-free cystic follicles in both ovaries. With the exception of SHBG and ovarian volume in hyperandrogenic subjects, all parameters returned to pretreatment values 3 months after discontinuation of the OC. 6 of the 9 oligomenorrheic subjects showed subjective improvement of skin problems; in addition, 6 reported a longterm decrease in hair growth. Post-treatment, oligomenorrhea and anovulation persisted in 7 of the 9 subjects. Although the effect of this treatment is temporary, the ethinyl estradiol-desogestrel OC appears to be effective in hyperandrogenic adolescents and may delay the progression of hirsutism and prevent adult micropolycystic ovarian disease.