Lars Fåhraeus

L‐norgestrel and progesterone have different influences on plasma lipoproteins

Abstract. Twenty‐six postmenopausal women wh had been on cutaneous oestradiol treatment for 3–6 months were given either 120 μg of l‐norgestrel (n= 13) or 300 mg of progesterone (n= 13) sequentially fc another 6 months. The concentrations of cholestero phospholipids and triglycerides were determined i plasma and in the HDL, HDL2, HDL3, LDL an VLDL fractions before and after one, three and si cycles of progestin treatment.

Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen

Objective  To screen for bacterial vaginosis (BV) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks (primary outcome).

Treatment with 2% clindamycin vaginal cream prior to first trimester surgical abortion to reduce signs of postoperative infection : A prospective, double-blinded, placebo-controlled, multicenter study

Background. Bacterial vaginosis (BV) and intermediate flora is known risk‐factor for postoperative infection after surgical termination of pregnancy. Vaginal application of 2% clindamycin cream is an efficacious treatment for BV, but it is not known whether preoperative administration of clindamycin cream might reduce the signs of post‐abortion infection after surgical termination of pregnancy.

Diagnosis of bacterial vaginosis: need for validation of microscopic image area used for scoring bacterial morphotypes

Background: The diagnosis of bacterial vaginosis (BV) is often made according to Nugent’s classification, a scoring system based on bacterial counting of Gram stained slides of vaginal secretion. However as the image area of the microscope field will influence the number of morphotypes seen there is a need to standardise the area. Methods: A graph intended for recalculation of number of bacterial morphotypes seen by the observer using 1000× magnification from various microscope set-ups was constructed and applied to data sets typical for scoring BV. The graph was used in recalculation of Nugent scores, which were also compared with the Ison/Hay scores to evaluate the consequences for the diagnosis of BV. Results: The observed image area differed by 300% among the investigated microscope set-ups. In two different data sets, one treatment study and one screening study, a considerable change in the number of women classified as intermediate was seen when the graph was used to standardise the image area. The recalculated numbers were also compared to the Ison/Hay classification. Weighted kappa indexes between the different methods were 0.84, 0.88, and 0.90, indicating that the methods are comparable. Conclusion: Because of the considerable differences among image areas covered by different microscope set-ups used in Nugent and Ison/Hay scoring, there is a need to standardise the area in order to reach comparable scores reflecting the diagnosis of BV in different laboratories. The differences in the intermediate group will have a considerable effect on the results from both treatment and prevalence studies, even though the kappa indexes indicate very good agreement between the methods used.

Predisposing factors for bacterial vaginosis, treatment efficacy and pregnancy outcome among term deliveries; results from a preterm delivery study

BackgroundBacterial vaginosis (BV) during pregnancy is associated with an increased risk of preterm delivery but little is known about factors that could predict BV. We have analyzed if it is possible to identify a category of pregnant women that should be screened for BV, and if BV would alter the pregnancy outcome at term; we have also studied the treatment efficacy of clindamycin.MethodsProspective BV screening and treatment study of 9025 women in a geographically defined region in southeast Sweden. BV was defined as a modified Nugent score of 6 and above. Data was collected from the Swedish Medical Birth Register. Women allocated to treatment were supplied with vaginal clindamycin cream. The main outcome goals were to identify factors that could predict BV.ResultsVaginal smears were consistent with BV criteria in 9.3%. Logistic regression indicates a significant correlation between smoking and BV (p < 0.001) and a greater prevalence of BV in the lower age groups (p < 0.001). We found no correlation between BV and history of preterm deliveries, previous miscarriages, extra-uterine pregnancies, infertility problems or reported history of urinary tract infections–factors that earlier have been associated with BV. Treatment with clindamycin cream showed a cure rate of 77%. Less than 1% of women with a normal vaginal smear in early pregnancy will develop BV during the pregnancy. There was no association between BV and the obstetric outcome among women who delivered at term. Women with BV, both treated patients and nontreated, had the same obstetric outcome at term as women with normal vaginal flora.ConclusionBV is more than twice as common among smokers, and there is a higher prevalence in the younger age group. However these two markers for BV do not suffice as a tool for screening, and considering the lack of other risk factors associated with BV, screening of all pregnant women might be a strategy to follow in a program intended to reduce the number of preterm births.

Profound alterations of the lipoprotein metabolism during danazol treatment in premenopausal women.

Twelve women with pelvic endometriosis were treated with 600 mg of danazol daily for 24 weeks. The molar and fractional lecithin:cholesterol acyl transfer (LCAT) rates and the concentrations of cholesterol, phospholipids, and triglycerides were determined in plasma and in the very low-density lipoprotein, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and HDL2 and HDL3 fractions before, during, and after the medication. After 2 weeks the HDL, HDL2, and HDL3 cholesterol concentrations were reduced by 49%, 73%, and 29%, respectively, while the LDL level was increased by 14%. The molar and fractional LCAT rates decreased during treatment, and these reduced LCAT rates are consistent with a reduced fractional LDL removal. Within 8 weeks after cessation of medication, all parameters had returned to the pretreatment levels.

Effects of the Estrogenicity of Levonorgestrel/Ethinylestradiol Combinations on the Lipoprotein Status

Abstract. Ninety‐eight women seeking contraceptive advice were randomly allocated to 6 months of treatment with one of the following four combinations of ethinylestradiol (EE) and levonorgestrel (NG): 20/250, 30/250, 30/150, and the so‐called triphasic drug. The EE/NG ratios were 0.08, 0.12, 0.20 and 0.36 respectively. Blood lipids, HDL‐cholesterol and sex hormone binding globulin (SHBG) were determined twice before treatment and after 1, 3 and 6 months of medication.

Plasma lipoproteins during and after danazol treatment

Abstract. Twelve women with pelvic endometriosis were treated with danazol, at a dose of 200 mg three times daily, over a 24‐week period. The concentrations of cholesterol and triglycerides were determined in plasma and in the lipoprotein fractions. After only 2 weeks the mean high density lipoprotein (HDL) cholesterol had already decreased by 49% and 6 weeks later the reduction was 59%. The low density lipoprotein (LDL) cholesterol concentration increased by 14% after 2 weeks and by 34% after 8 weeks. The triglycerides increased by 20% after 2 weeks. Eight weeks after cessation of treatment the lipoprotein fractions had returned to the pretreatment levels.

Metabolic consequences of postmenopausal estrogen and progestogen treatment.

Postmenopausal estrogen deficiency symptoms such as sweatings and hot flushes are usually treated with estrogens taken orally. In Sweden today, this is the only route of administration that is available for systemic estrogen treatment. I will therefore discuss mainly the metabolic consequences of oral medication, although during recent years increasing interest has been attracted by other routes of estrogen administration such as percutaneous or vaginal application. These routes give different metabolic responses from oral treatment. In the foilowing I will only consider the effects of postmenopausal replacement treatment on lipid and glucose metabolism, on blood coagulation and on the mineral content of bone. The reason for the great interest in the effects of hormonal treatment on plasma lipoproteins is the well-known differences in incidence of cardiovascular diseases between men and women. Endogenous and exogenous sex steroids influence the distribution of the plasma lipoproteins and may thereby influence the incidence of coronary heart disease (CHD). Before puberty the mean lipid and lipoprotein levels between boys and girls are equal. After puberty the level of high density lipoprotein (HDL) is lower and the levels of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) are higher in men than in women. After the menopause there is a rapid increase in the LDL, while the HDL remains mainly unchanged. Epidemiological studies have demonstrated that the concentration of LDL-cholesterol (C) is directly correlated to and the concentration of HDL-C is inversely correlated to the risk of developing CHD. Oral treatment with estrogens raises the HDL level, apparently in a dose-related manner (1). The increase

Authors response to: Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen

OBJECTIVE To screen for bacterial vaginosis (BV) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks (primary outcome). DESIGN Randomised consent design for clinical trials according to Zelen. SETTING Southeast region of Sweden. POPULATION A total of 9025 women were screened in early pregnancy. METHODS A total of 819 women with a Nugent score of 6 and above were considered to have BV and treated according to Zelen allocation. The incidence of late miscarriage and spontaneous (noniatrogenic) preterm birth was assessed. MAIN OUTCOME MEASURES Late miscarriage and spontaneous preterm delivery before 37 weeks. RESULTS Therapy with vaginal clindamycin had no significant impact on the incidence of spontaneous preterm delivery prior to 37 completed weeks; OR 0.90, 95% CI 0.40-2.02 (primary outcome variable). However, only 1 of 11 women in the treatment group versus 5 of 12 in the control group delivered prior to 33 completed weeks; OR 0.14, 95% CI 0.02-0.95. Treatment was associated with 32 days longer gestation for the 23 participants who had late miscarriage or spontaneous preterm birth (P= 0.024, Mann-Whitney U test) and significantly fewer infants had a birthweight below 2,500 g (secondary outcome). A follow up of infants born preterm 4 years postnatally indicated that extending gestational age did not increase the number of sequelae. CONCLUSIONS Clindamycin vaginal cream therapy was associated with significantly prolonged gestation and reduced cost of neonatal care in women with BV. Early screening for BV and treatment with clindamycin saved approximately 27 euro per woman.