Helena Sundström

Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study

Objective: Nonhormonal treatment of postmenopausal symptoms is a subject of great interest today. The results of studies on selective serotonin reuptake inhibitors (SSRIs) are promising, but long-term results do not exist. The objective of this study was to evaluate the efficacy of citalopram and fluoxetine in the treatment of physical and psychological menopausal symptoms and their effects on psychosocial and sexual well being in symptomatic postmenopausal women. Design: One hundred fifty healthy women suffering from menopausal symptoms were recruited to this placebo-controlled double-blind study with a follow-up period of 9 months. They were randomized into three groups receiving placebo, fluoxetine, or citalopram. The initial dose was 10 mg of both fluoxetine and citalopram, and it was increased to 20 mg at 1 month and to 30 mg at the 6-month visit. The main outcome measures were hot flushes and Kupperman index. The RAND-36 Quality of Life questionnaire, Becks Depression Scale, and the McCoy Female Sexuality Questionnaire were used at every control visit. Results: There were no statistically significant differences between the groups in respect to number of hot flushes, Kupperman index, or Becks Depression Scale, although there was a tendency in all these parameters in favor of SSRIs versus placebo. Insomnia improved significantly in the citalopram group versus placebo. Discontinuation rates at nine months were 40% in the placebo group, 34% in the fluoxetine group and 34% in the citalopram group. Conclusions: Compared with placebo, citalopram and fluoxetine have little effect on hot flushes and cannot therefore be recommended for the treatment of menopausal symptoms, if vasomotor symptoms are the main complaint. Whether the improvement of insomnia by means of citalopram affects the quality of sleep needs further investigation.

Serum selenium and glutathione peroxidase and plasma lipid peroxides in uterine ovarian or vulvar cancer and their responses to antioxidants in patients with ovarian cancer

The concentrations of serum selenium and plasma lipid peroxides, and the activity of serum glutathione peroxidase (GSH-Px) were measured before any therapy in patients suffering from uterine, ovarian or vulvar cancer, and in association with 1-day combination cytotoxic chemotherapy of ovarian cancer following 1-week supplementation with selenium (96 micrograms/day), vitamin E (300 mg/day), selenium and vitamin E, or placebo. Patients with gynaecological cancer (N = 44) had lower serum concentration of selenium (1.15 +/- 0.04 S.E. mumol/l; P less than 0.05) and serum activity of GSH-Px (404 +/- 13 units/l, P less than 0.01) than the control subjects (N = 56; 1.25 +/- 0.03 mumol/l and 444 +/- 8 units/l, respectively). In association with cytotoxic chemotherapy selenium alone (P less than 0.05), vitamin E alone (P less than 0.05) and both of them together (P less than 0.001) decreased the plasma concentration of lipid peroxides, and the combination of selenium and vitamin E also increased the activity of serum GSH-Px (P less than 0.01). During placebo, cytotoxic chemotherapy did not affect plasma lipid peroxides but it decreased (P less than 0.001) the activity of GSH-Px. Selenium inhibited this effect. Our data suggest that antioxidative mechanisms of patients with gynaecological cancer may be defective and that treatment with selenium and vitamin E results in changes of biochemical factors related to lipid peroxidation.

Comparison of three serum assays for bone collagen formation during postmenopausal estrogen–progestin therapy

Postmenopausal hormone replacement therapy (HRT) lowers the turnover rate of the mineralized bone matrix, the predominant organic component of which is type I collagen. The effect of estrogen on bone metabolism has been monitored by measuring the circulating concentration of the carboxy-terminal propeptide of type I procollagen (PICP), which decreases during HRT. We have recently developed assays for the intact amino-terminal propeptide (PINP) of type I procollagen, a protein set free from the other end of the same gene product. PICP and PINP, both derived from the synthesis of type I collagen, but differing in their further metabolism, were assessed in 47 postmenopausal women, aged 45-66 years, undergoing postmenopausal HRT. Estradiol-gel applied daily was combined to a continuous progestin administered by three different routes. Serum samples obtained before the treatment and 6 and 12 months after its commencement were analyzed for PICP, PINP, PINP Col 1 (assay variant measuring also the degradation product of PINP) and PIIINP (amino-terminal propeptide of type III procollagen). During HRT the circulating concentration of PICP decreased by 20%, that of PINP by 42% and that of PINP Col 1 by 32% in 12 months. The correlation between the two propeptides, which was 0.676 before the treatment, increased to 0.851 in 6 months and to 0.815 in 12 months. The correlations between PINP and PINP Col 1 were 0.872 before the treatment and increased to 0.925 and 0.941 after 6 and 12 months of treatment, respectively. The serum concentration of PIIINP, which reflects the turnover of the soft tissue collagens, did not change remarkably. Our findings indicate that the intact PINP is a more dynamic marker of bone metabolism than PICP and can therefore be recommended as a marker reflecting the effect of estrogen on bone collagen formation during HRT.

The role of mediolateral episiotomy during labour. Analysis of risk factors for obstetric anal sphincter tears

Background. To determine risk factors for third‐degree and complete third‐ or fourth‐degree anal sphincter tears in vaginal delivery.

Percutaneous estradiol gel with an intrauterine levonorgestrel releasing device or natural progesterone in hormone replacement therapy

OBJECTIVE To evaluate the bleeding patterns and clinical compliance associated with postmenopausal amenorrhea-inducing forms of hormone replacement therapy using either percutaneous estradiol-gel and a levonorgestrel-releasing intrauterine device or an oral/vaginal natural progesterone. METHODS Sixty postmenopausal women with an intact uterus were followed over 12 months in this open, non-randomised, parallel group study. All patients continuously received a gel containing 1.5 mg of estradiol daily. The women were divided into three groups on the basis of progestin administration. Twenty women (group I) had a levonorgestrel-releasing device (LNG-IUD) inserted at the beginning of the study. Twenty-one women (group II) received oral natural micronised progesterone (oral P) 100 mg daily during 25 calendar days each month, and 19 women (group III) used vaginal natural micronised progesterone (vaginal P) 100-200 mg daily during 25 calendar days each month (higher dose if spotting occurred). Clinic visits were at 0, 3, 6 and 12 months. Bleeding patterns were recorded by the patient in a diary and clinical compliance was evaluated at control visits during the treatment. Symptoms were recorded using a modified Kuppermann index. The serum estradiol concentration was determined at the 0, 6 and 12 month control visits. RESULTS 80% (n = 16) of the patients in the LNG-IUD group, 67% (n = 14) in the oral P group II and 53% (n = 10) in the vaginal P group were without bleeding at 12 months. Spotting was common during the first 3 months. Symptom relief was good in each group. The LNG-IUD did not cause any serious side-effects. Compliance was good for LNG-IUD and oral progesterone but not for vaginal progesterone. CONCLUSIONS Percutaneous estradiol-gel associated with LNG-IUD is an appropriate method of hormone replacement therapy. The combination of oral natural progesterone with estradiol-gel is also useful, although bleeding episodes complicated the treatment in one third of the patients. The vaginal administration of natural progesterone was impractical due to bleeding disorders.

Insulin-like growth factor-binding protein-1 : a biochemical marker of endometrial response to progestin during hormone replacement therapy

OBJECTIVES To compare immunohistochemical localization of insulin-like growth factor binding protein-1 (IGFBP-1) in endometrial stromal cells with endometrial morphology during three regimens of continuous combined hormone replacement therapy. METHODS Endometrial samples for morphological examination and immunohistochemical staining with monoclonal antibody against IGFBP-1 were obtained from 30 menopausal women before treatment and after 12 and 24 months of continuous combined hormone replacement therapy. All women received percutaneous estradiolgel releasing 1.5 mg estradiol daily. Regarding progestins, patients were divided into three groups: one group (n = 15) had a 20 micrograms/24 h levonorgestrel-releasing intrauterine device (LNG-IUD); the women in the other two groups received micronised natural progesterone either 100 mg orally (n = 7) or 100-200 mg vaginally (n = 8) daily, 25 days per calendar month. RESULTS Before treatment the endometrium of all women was atrophic or subatrophic and no IGFBP-1 could be detected in any of the samples which contained enough stromal cells for evaluation. After 12 and 24 months of treatment, epithelial atrophy with decidual transformation in stroma was detected in all specimens in the LNG-IUD group, and IGFBP-1 was localized in decidualized stromal cells in all samples. In the other two groups, no signs of progestin effect were detected by microscopic examination in any of the endometrial samples and IGFBP-1 staining was completely negative in all of them. CONCLUSION A striking difference occurred in both morphological and biochemical response in the endometrium of women treated with LNG-IUD compared with those receiving oral or vaginal micronised progesterone during continuous combined HRT. Micronised progesterone at doses used in this study turned out to be ineffective to prevent the proliferative effect of estrogen. Immunohistochemical localization of IGFBP-1 in endometrial stromal cells strongly correlated with decidual reaction in all endometrial specimens exposed to LNG-IUD, suggesting that the immunostaining of IGFBP-1 can be used as a means of assessing the strength of progestin effect in the endometrium during HRT.

Endometrial morphology during hormone replacement therapy with estradiol gel combined to levonorgestrel-releasing intrauterine device or natural progesterone.

OBJECTIVES To evaluate endometrial responses to three different forms of amenorrhea-inducing HRT in postmenopausal women. MATERIAL AND METHODS Fifty-one postmenopausal women completing a one-year HRT trial with percutaneous estradiol gel containing 1.5 mg estradiol daily combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) (n=18), or natural progesterone 100 mg daily orally (n= 19) or vaginally (n=15) during 1-25 calendar days of each month. Endometrial thickness and uterine size were measured by transvaginal ultrasound, and endometrial cytology/histology was assessed from specimens taken by needle aspiration before the study and at 12 months. RESULTS Before medication, the median endometrial thickness was 2.0 mm in the LNG-IUD group, 2.4 mm in the oral P group and 2.5 mm in the vaginal P group. At 12 months of therapy the respective values, 3.0, 2.7 and 2.4 mm, did not differ significantly from the initial values. LNG-IUD induced epithelial atrophy in all women, which was accompanied by stromal decidualization in 12 women. On the contrary, only four women in the oral P group and five women in the vaginal P group had an inactive or atrophic endometrium. The remaining cases were dominated by proliferative features. No hyperplasia was seen in any of the groups. CONCLUSION LNG-IUD appeared to be an effective method of counteracting the stimulatory effect of estrogen on the endometrium, whereas natural progesterone given orally or vaginally was not sufficiently effective in this function at the doses used. The vaginal and oral administrations of progesterone did not differ from each other in this respect.

Low serum selenium concentration in patients with cervical or endometrial cancer

Serum concentrations of selenium were determined in 37 patients with cervical and 64 patients with endometrial cancer. The patients had lower (P < 0.001) serum concentrations of selenium than the age‐, weight‐ and place of residence‐matched paired control women. There was no difference in the selenium concentration between various age groups or different clinical stages of cervical or endometrial cancer. A low serum concentration of selenium might be a contributing factor in uterine carcinogenesis.