The effect of 17beta-estradiol at doses of 0.5, 1 and 2 mg compared with placebo on early postmenopausal bone loss in hysterectomized women.

In a randomized double-masked placebo-controlled parallel-group trial 166 hysterectomized (+/- oophorectomy) perimenopausal and postmenopausal women aged 45-55 years with a follicle stimulating hormone level above 20 IU/l were treated with one daily dose of either 0.5 mg 17beta-estradiol (E2), 1 mg E2, 2 mg E2 or placebo for 2 years. Bone mineral density (BMD) and biochemical bone markers were determined. All three doses of E2 were significantly better than placebo with respect to change in BMD at the lumbar spine (L1-L4) (p<0.0001 for all pairwise comparisons) and hip (femoral neck, trochanter, Ward's triangle). The mean percentage change from baseline at the lumbar spine was -0.2%, 0.8% and 1.8% in the 0.5, 1 and 2 mg E2 groups respectively compared with -3.5% in the placebo group. Both 1 and 2 mg E2 were significantly better than placebo in increasing the BMD at the femoral neck (p<0.001), trochanter (p<0.01) and Ward's triangle (p<0.0001), while 0.5 mg E2 was significantly better than placebo at the femoral neck (p<0.001) and Ward's triangle (p<0.0001). The overall difference in mean percentage change in BMD at the femoral neck versus placebo (-0.2%) was 3.8% for 0.5 mg, 4.0% for 1 mg and 3.9% for 2 mg E2; the corresponding numbers for trochanter were 1.3%, 3.3% and 3.2%, respectively, and -2.2%,, 2.9, 2.9% and 4.0%, respectively, for Ward's triangle. More than half the women who received placebo presented with a decrease in BMD at the hip. The percentage of women in the 0.5 mg E2 group who maintained or increased BMD at the femoral neck, trochanter and Ward's triangle was 69%, 56% and 44%, respectively. For 1 mg E2 the numbers were 69%, 78% and 61% respectively, and for 2 mg E2 were 59%, 68% and 59% respectively. Osteocalcin, serum pyridinium crosslinks, urinary pyridinium cross-links and urinary hydroxyproline/creatinine decreased significantly (p<0.0001, p<0.05) in the 0.5, 1 and 2 mg E2 groups compared with the placebo group after 6 and 24 months of treatment.

A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms.

OBJECTIVE: To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability. DESIGN: Double-blind, randomised controlled trial. SETTING: Twenty-nine sites in Denmark, nine in Norway and six in Sweden. PARTICIPANTS: Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy. INTERVENTIONS: Daily treatment with tibolone 2.5 mg (n = 218) or 17beta-oestradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA) (n = 219). MAIN OUTCOME MEASURES: Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12, 24 and 48 weeks. RESULTS: Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E2/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E2/NETA (P < 0.0001), mainly during the first six treatment cycles. CONCLUSIONS: Both tibolone and E2/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding.

Failure to predict and attempts to explain urinary stress incontinence following vaginal repair in continent women by using a modified lateral urethrocystography.

Of continent women undergoing the Manchester procedure for genito-urinary prolapse, about 25% develop urinary stress-incontinence. In order to study whether this is due to pre-existing anatomical factors or to the surgical procedure itself, a prospective study was set up. Fifty-eight continent women operated on for genito-urinary prolapse, underwent urethrocystography prior to and 3 months following surgery. Sixteen of the 58 (28%) developed stress-incontinence following the operation. Radiological parameters preoperatively were of little help in distinguishing the patients developing incontinence from those remaining continent. The stress-incontinence following a Manchester procedure for genital prolapse seems to depend on two surgical factors: an insufficient elevation of the bladder-neck and a radical reduction of the cystocele. A parameter combining the two factors: the percentage reduction of the cystocele minus the percentage elevation of the bladder-neck, was significantly lower in women remaining continent than in those who developed stress-incontinence.

The risk of developing urinary stress-incontinence after vaginal repair in continent women. A clinical and urodynamic follow-up study.

A study was performed to find out how often continent women develop urinary stress-incontinence after a Manchester operation for genito-urinary prolapse, and to ascertain whether factors in the selection of patients, or steps in the surgical procedure are responsible for producing stress-incontinence postoperatively. Seventy-three of 102 consecutive patients were continent before operation. Sixteen of the 73 women (22%) became stress incontinent. Advanced age increased the risk of developing urinary stress-incontinence. Twenty-five per cent of the women more than 60 years old developed stress-incontinence, but only 1 of 13 below the age of 60. Preoperative urethral closure pressure was significantly lower in those developing urinary stress-incontinence, and closure pressure was further reduced by surgery in this group, significantly more than in the women remaining continent. Surgery significantly reduced the pressure transmission ratio in the patients who developed urinary stress-incontinence, and less in the continent ones. The preoperative pressure transmission ratio, however, was not related to the risk of developing urinary stress-incontinence after the operation. The urodynamic examinations pre- and postoperatively demonstrated important changes in the urodynamic parameters produced by the Manchester procedure, but did not prove useful in determining which patients will develop urinary stress-incontinence.

Fiber-optic versus microtip transducers in simultaneous urethrocystometry. A comparative study.

A comparative study of a new fiber-optic transducer versus a microtip transducer was performed in 13 females. A good correlation was found on bladder pressure. The urethral pressure diverged considerably, as the pressures measured with the fiber-optic transducer were about two thirds of the pressures found with the microtip. The functional urethral length measured with the fiber-optic transducer was also shorter.

The function of the urethral blood flow in maintaining urinary continence. A preliminary report.

Urethral pressure is made up of three components, equal in size: the striated muscle component, the smooth muscle component, and the vascular component. Anti-embolism stockings have been helpful in bringing about significant improvement in blood flow through the lower extremities. A pilot study was undertaken with 15 women to find out whether or not the same approach led to increase in urethral pressure. Simultaneous urethrocystometry was applied to women with and without stockings. Significant rise in urethral pressure was recorded from women with urinary stress incontinence who used stockings. Four of eight incontinent women were improved to continence by means of stockings.

A double-blind, cross-over study of the effects of terodiline in women with unstable bladder.

In a double-blind, cross-over study, the effects of terodiline were evaluated in 12 women with motor urge incontinence. The patients were investigated by simultaneous urethro-cystometry before and after treatment fo 2-week periods with placebo and terodiline 12.5 mg twice daily. The effects on subjective symptoms were also assessed. In all patients but one, terodiline increased the bladder capacity and also the bladder volume at which urgency was experienced. No effects on the urethral pressure profile or residual urine were found. Subjective improvement was reported by all but one of the patients. Placebo treatment had no effect on the measured parameters or on the subjective symptoms. No side effects were reported during any of the treatment periods. --It is concluded that terodiline can be used for treatment of female motor urge incontinence, and that it is a promising alternative to drugs presently used for this disorder.

Factors maintaining the intraurethral pressure in women.

To determine the components of the intraurethral pressure at rest, five continent women were studied with simultaneous urethrocystometry, including urethral pressure profile measurements, before, during and after curarization, as well as after clamping of the arterial blood supply to the urethra. The results showed that the striated muscle component in the urethra and pelvic floor is responsible for one-third of the total intraurethral pressure. Another one-third is exerted by the urethral vascular bed. The remaining one-third is most probably attributable to the smooth musculature and connective tissues in the urethra and the periurethral tissues.

The effects of estrogens and gestagens on the urethral pressure profile in urinary continent and stress incontinent women.

The present investigation was performed to study the urodynamic effects of hormones on the lower urinary tract in women. Twenty-four stress incontinent and 6 continent women were randomly given E2 and E3 orally in doses of 4--8 mg per day for 3 weeks. Another group of 8 women were given a single i.m. injection of 1000 mg gestagen. All the women were examined with simultaneous urethrocystometry, including urethral pressure profile measurement, before and after treatment. After estrogen treatment the transmission of intraabdominal pressure to the urethra increased. Furthermore, there was a significant increase in maximum urethal pressure and urethral length at rest. After gestagen treatment no significant changes of the recorded parameters were observed.

Urethral pressure profile in continent women from childhood to old age.

One hundred and sixty-nine urinary continent females were examined with simultaneous urethro-cystometry, using a dual microtip-catheter. It was shown that the maximum urethral pressure and the urethral length increased from infancy to the age of 20--25 years. Thereafter, the values of these parameters decreased with increasing age. The bladder pressure remained constant in the different age groups. In six women, aged between 20 and 25 years, the parameters were measured three times during a menstrual cycle. No correlation between the fluctuating estrogens, gestagens, catecholamines and the urethral pressure or the urethral lengths was found.

Terodiline inhibition of human bladder contraction. Effects in vitro and in women with unstable bladder.

Terodiline, a drug with anticholinergic and calcium antagonistic properties, effectively relaxed carbachol-contracted, isolated human bladder preparations. In the concentrations used, terodiline displaced to the right the concentration-response curve obtained on cumulative addition of carbachol. The maximum response was slightly reduced only at the highest terodiline concentration used (5 microM), suggesting a mainly competitive antimuscarinic effect. Nine patients, aged 12--78 years, suffering from urge urinary incontinence were investigated by simultaneous urethro-cystometry before and after treatment with terodiline 12.5 mg twice or three times daily for 10 days. The patients reported subjective improvement with almost no side effects. Objectively, the number of uninhibited bladder contractions and the amplitude of the contractions decreased. The bladder capacity was almost doubled. There were no marked effects on bladder and urethral pressures at rest, and only two of the investigated patients had slight residual urine after treatment. The results suggest that terodiline is a promising alternative to existing drugs for inhibition of undesired detrusor activity.

Effects of nifedipine in women with unstable bladders.

A study of the effect of the calcium antagonist nifedipine on the detrusor contractions of 10 women with an unstable bladder is reported. An inhibiting effect was observed in all patients after intake of nifedipine. The number of contractions and the contraction amplitudes decreased, and the bladder capacity increased. Resting intraurethral and intravesical pressures were not affected. Subjective improvement was reported by all patients during a week of continuous nifedipine treatment. Side effects were few and tolerable. It is suggested that nifedipine can be of value in the treatment of unstable bladder.

Initiation of micturition: a study of combined urethrocystometry and urethrocystography in healthy and stress incontinent females.

Six continent and 4 incontinent females were examined by a combined technique of simultaneous urethrocystometry and rapid X-ray-film exposures. The study confirmed that pressure changes occurring in the urethra and bladder at initiation of voiding were not caused by artefacts of the measuring technique. It was found that the continent females initiated micturition mainly by a rapid decrease in urethral pressure followed by an increase in the bladder pressure. The stress incontinent females strained out the urine without initial urethral relaxation. Since the X-ray-technique did not add any new clinical information about micturition in females the pressure recording technique is recommended for routine investigation of micturition in females.

Effects of nifedipine on the smooth muscle of the human urinary tract in vitro and in vivo.

Smooth muscle preparations of the urethra, bladder, and ureter were obtained from patients undergoing operations for various urological disorders. The urethral preparations were contracted by noradrenaline (0.1-3 microgram . ml-1), prostaglandin F2alpha (1-10 microgram . ml-1), and potassium (127 mM), the bladder preparations by carbacholine (0.004-1 microgram . ml-1), prostaglandin F2alpha (1-10 microgram . ml-1), potassium (127 mM), and barium chloride (3 mM), and the ureter preparations by potassium (127 mM), and barium chloride (3 mM). Irrespective of the mode of activation, pretreatment with nifedipine (0.1 microgram . ml-1) for 10 min. reduced the responses. Nifedipine also relaxed preparations contracted by the contractile agents used. In 19 female patients, aged 20 to 73 years, undergoing investigation because of urgency and/or urge incontinence, simultaneous urethrocystometry at rest was performed before and after oral administration of 20 to 40 mg nifedipine. Bladder capacity and residual urine were also determined. Nifedipine did not affect the pressures within the bladder and urethra, nor did it increase the bladder capacity. However, after nifedipine intake there was a statistically significant increase in residual urine. The results suggest that nifedipine can inhibit contractile activity induced by drugs with different modes of action; the drug does not affect the tone in bladder and urethra.

Initiation of voiding in healthy women and those with stress incontinence.

Sixteen healthy women, and 13 with stress incontinence were investigated by simultaneous urethrocystometry during the initiation of voiding. In the healthy women, there was a decrease in the maximum intra-urethral pressure immediately before micturition. A few seconds later (mean 3.0 sec), the intravesical pressure increased. As a result, the urethral closure pressure decreased to zero, and urine started to escape from the urethra. In the patients with stress in continence, three different ways of initiating micturition were observed. Five patients initiated voiding by the Valsalva manoeuvre, 3 mainly by decreasing the maximum urthral pressure, and 5 mainly in the same way as the healthy women. The results suggest that preoperative analysis of the micturition pattern by means of simultaneous urethrocystometry can be of value for the choice of operative procedure, and thereby make it possible to avoid or reduce postoperative retention of urine.