A continuous infusion technique of either [3H]oestradiol-17 beta (E2) or unlabelled E2 was used to investigate suggested differences in the metabolic clearance rate of oestradiol-17 beta (MCR-E2) in immature and peripubertal female pigs. Using the isotope infusion technique, the following values were obtained: 60 day old gilts; MCR-E2 = 2133 +/- 274 (mean +/- SEM) ml/min, MCR-E2/kg BW = 116 +/- 14.5 ml/min kg, and conversion ratio (CR) of E2 to oestrone (E1) = 31.6 +/- 3.7%. The respective values for 160 day old gilts were: MCR-E2 = 3027 +/- 340, MCR-E2/kg BW = 48.5 +/- 4.82, and CR = 15.9 +/- 2.12. Except for a significant difference in the weight related MCR-E2 data for the 60 day old group, similar values were found following infusion of unlabelled E2. The percentage of radioactivity extractable with ether from plasma was 22.6 +/- 3.0% and 27.2 +/- 2.0%. Fifty-seven and 66% of total radioactivity infused was recovered in the urine within 12 h in 60 and 160 day old gilts, respectively. There was no difference in the percentage binding of E2 to plasma proteins as determined by equilibrium dialysis (80%). It is concluded that in addition to an activation of ovarian steroido-genesis during puberty, a gradual maturational decrease in the MCR-E2/kg VW might play a role in raising plasma E2 concentrations and thus in constituting an effective oestrogen feedback signal, which results in the first pre-ovulatory LH-surge.

A non-invasive study of urinary hormones in 6 captive female Goeldi's monkeys provided accurate information on reproductive function. Conjugated oestrone accounted for 80-85% of the urinary oestrone and oestradiol measured. Radioimmunoassay measurements of conjugated oestrone provided a reliable indicator of cyclic ovarian function (mean cycle length: 24.1 +/- 0.9 days; n = 9) and pregnancy (gestation: 145, 155 days; n = 2). Measurements of urinary progesterone and pregnanediol glucuronide were only reliable as indicators of ovarian cyclicity. Elevations in urinary conjugated oestrone coincided with luteal-phase elevations of urinary progesterone and pregnanediol glucuronide. Urinary LH concentrations provided no indication of pituitary activity. However, the frequencies of female sexual solicitations of males were maximal when oestrone conjugate concentrations rose, suggesting a peri-ovulatory period. Ovulation was suppressed in 1 of 3 subordinate females housed in male-female-female trios.

Six ovariectomized women with the uterus left in situ were given a daily oral dose of 0.5 mg of oestradiol decaneoate in oil for 14 days. After a single dose of oestradiol decanoate mean plasma oestradiol rose from 26.8 pg/ml to 66.8 pg/ml within 30 min. There was a further rise to 100-110 pg/ml (P less than 0.001) remaining at the same level over a 24 h period. On repeated daily administration of oestradiol decanoate this rise continued reaching the mean value of 187.1 pg/ml (P less than 0.001) at 2 weeks, while plasma oestrone remained at the same level (147.1 pg/ml) as it was at 24 h. The ratio of plasma oestrone:oestradiol was less than 1 at 2 weeks. Plasma FSH and LH fell progressively during the medication. Changes of the Maturation Index, cervical mucus Ferning and Spinnbarkeit demonstrated the strong 'peripheral' activity of this dose of oestradiol decanoate. All endometrial specimens showed late proliferative changes at 2 weeks. It was concluded that the favourable properties of oestradiol decanoate offer new possibilities for a more physiological oestrogen supplementation therapy.

Serum FSH, LH and oestrone levels were determined in postmenopausal women before and at 1, 3 and 6 months after the onset of cyclical treatment with 0.05 mg of ethinyl oestradiol (n = 19) or 2 mg of oestradiol valerianate (n = 20). Most samples from the women taking oestradiol valerianate were also analyzed for oestradiol. Vaginal smears were obtained from all patients. Although all women were relieved of vasomotor symptoms, the FSH levels usually exceeded the fertile range. Ethinyl oestradiol reduced FSH by 70 to 75 per cent and LH by 30 to 40 per cent while oestrone was increased by 20 to 40 per cent. In the women taking oestradiol valerianate, FSH and LH levels were both reduced by 20 to 25 per cent wheras serum oestradiol increased by 200 to 300 per cent and oestrone increased by 600 to 700 per cent. The mean vaginal maturation value rose equally in the two groups but 40 per cent of the patients in both groups showed no change in the value. There was no correlation between the appearance of vaginal endocrine smears and hormone levels.

An intravenous injection of 50 mg dehydroepiandrosterone was given to 19 women at the 38th week of pregnancy. The concentration of androstenedione, testosterone, oestradiol and oestrone in plasma was measured at intervals following the injection. The concentration of androstenedione and testosterone rose rapidly; reaching a peak after 10 minutes and returning to near baseline level by 30 minutes. Oestradiol rose more slowly, reaching a peak after 45 minutes and being sustained at high levels for 3 1/2 hours before returning slowly to baseline. Oestrone rose yet more slowly and did not reach a peak until 2 1/2 hours after the injection. It is concluded that the steroid responses are too variable from one individual to another for this test to be useful in the clinical assessment of fetal wellbeing but that it was likely to be a powerful tool in the investigation of placental steroid biogenesis.

The extraneuronal removal and disposition of noradrenaline in rabbit dental pulp was examined in view of earlier evidence that the tissue possessed an extraneuronal uptake process resembling neuronal uptake1. Pulp, which had been depleted of sympathetic nerves by homolateral superior cervical ganglionectomy, was incubated in vitro with 3H-noradrenaline in low concentrations (0.025 or 0.18 mumol/l). When the metabolising enzymes (monoamine oxidase, catechol-O-methyl transferase) were active, 3H retention by the denervated pulp, as indicated by the 3H content after the tissue had been washed for 30 min following incubation with 3H-noradrenaline, was less than 3% of that of the innervated pulp. When the enzymes were inhibited, retention rose to approximately 30% of that of the innervated pulp. Analysis of the time course of the 3H efflux indicated that the 3H-noradrenaline in the denervated pulp had accumulated in a single compartment characterised by a t1/2 for efflux of several hours. Accumulation did not occur under Na(+)-free conditions, and was inhibited by desipramine (IC50 less than 0.03 mumol/l) and by substrates of neuronal uptake1. Mean IC50 values of the latter were very similar to those for inhibition of neuronal uptake1 and comprised (in mumol/l): (+)amphetamine (0.29), dopamine (0.31), tyramine (0.39), (-)noradrenaline (0.70), (-)adrenaline (1.50), 5-hydroxytryptamine (20) and bretylium (35). Uptake2 inhibitors were less active (O-methyl isoprenaline, IC50 = 60 mumol/l) than uptake1 inhibitors, or were without inhibitory effects at the concentrations tested (hydrocortisone, 210 mumol/l; 2-methoxy oestrone, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the direct effects of cyproterone on the ovarian biosynthesis of steroids, tissue slices obtained from two cyclically functional human ovaries were incubated with [4-14C]pregnenolone as precursor. The steroid production was determined by measuring the concentration of eleven 14C-labelled steroids in the medium at the end of a 3-h incubation. Under control conditions, the in vitro-synthesis of 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, androstenediol (5-ene-3 beta-hydroxy-steroids) and androstenedione represents the characteristic profile of steroids of the ovary from the follicular phase. The addition of cyproterone to the incubation medium inhibited the biosynthesis of androstenedione, whereas 17 alpha-hydroxypregnenolone and dehydroepiandrosterone increased. The in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, oestrone and oestradiol-17 beta represents the characteristic profile of steroids of the luteal ovary. The biosynthesis of progesterone, 17 alpha-hydroxyprogesterone and oestradiol-17 beta is inhibited by cyproterone. The principal manifestation of the effects of cyproterone on the two different profiles of steroids is an apparent inhibition of the 3 beta-hydroxysteroiddehydrogenase-delta 5-4-isomerase activity. It is noteworthy, that the effects of the "pure antiandrogen" cyproterone are similar to those effects previously published for progestagens (chlormadinone acetate, norethisterone acetate and D-norgestrel). A simplified concept of the direct effects of cyproterone and progestagens on the steroidogenesis in the human ovary is proposed. The results indicate, that cyproterone, in addition to its well-known androgen receptor blocking effect, act directly on the steroid biosynthesis in the human ovary in vitro.

In this study, hormone profiles were studied using Diane 35 and Diane 50 before and after treatment for 4-25 months. A comparison of the hormone profiles with Diane 35 or Diane 50 should investigate, if both preparations induce complete ovarian suppression, independent of the given dose of ethinyl oestradiol. 43 patients were treated with Diane 35 and 15 women with Diane 50 over a different lengths of time--up to a period of 25 cycles. Parallel to the determination of the hormone profiles (luteinising hormone [LH], follicle stimulating hormone [FSH], prolactin, oestrone [E1], oestradiol [E2], progesterone, total testosterone [T. T.], free testosterone [F. T.], dehydroepiandrosterone-sulfate [DHEA-S], delta-4-androstenedione [A.] and sex hormone binding globulin [SHBG]), observations on the androgen symptoms before treatment and their course during therapy were made. Moreover, the ratios of LH/FSH and E1/E2 as well as the androgenic index, the ratio of total testosterone/SHBG were determined as control of treatment effects. The most important hormonal changes, which had been observed during a period up to two years are the following: --LH and FSH suppression--prolactin with increasing tendency--decrease of the total androgens and free testosterone-- decrease of the oestrogens E1, E2--increase of SHBG. The confirmation of the efficacy of the anti-androgen/oestrogen combination was reflected by the decline of the androgenic index in all groups. Acne and seborrhoe improved after 3-4 cycles; alopecia after 8-9 cycles and hirsutism diminished after 3 cycles of treatment. In spite of different doses of the combined preparations with 2 mg cyproteronacetate and 0.035 or 0.050 mg ethinyloestradiol, no difference in ovarian suppression as well clinical effects could be found.

For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291 and its derivatives, a variety of endocrine characteristics were studied. (1) Androgenic and anabolic activity : Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328, to the immature orchiectomized rat resulted in significant weight increase of the levator ani but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity : Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17 beta. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17 beta. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity : Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17 beta was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 microgram oestrone in the adult ovariectomized rat. (4) Progestational activity : These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity : Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity : Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate and placebo which had success rates of 76 and 74% respectively. However, the relative advantage of ethinyl oestradiol was marginal, with an average reduction of 1 bleeding day and 3 spotting days compared with the other two groups. Immediately after treatment, women given ethinyl oestradiol had less bleeding but a more unpredictable pattern than the other two groups. In the long term, there were no differences between the bleeding patterns or the discontinuation rates for any reason in the three groups, and the most important single reason for discontinuation in those groups remained 'menstrual problems'. In summary, the study showed that treatment of DMPA-induced prolonged bleeding with ethinyl oestradiol had a limited short-term effect but no beneficial effect on the acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate was no different from placebo.

Oestradiol-17 beta and conjugated oestrone, oestradiol-17 beta and oestradiol-17 alpha were measured in peripheral plasma of heifers treated with PMSG/PGF-2 alpha to induce superovulation. Changes in the concentrations of each hormone were synchronous, the highest level being near oestrus. For a given number of ovulations the hormone with the highest concentration was total oestradiol-17 alpha, then came total oestrone, total oestradiol-17 beta and oestradiol-17 beta. For each oestrogen, the maximum preovulatory concentration measured was significantly correlated with the number of ovulations; the regression line for total oestradiol-17 alpha was twice as steep as that for oestradiol-17 beta. It is concluded that in animals treated to induce superovulation assay of total oestradiol-17 alpha gives a better induction of the number of follicles induced to ovulate than does the more conventional assay of oestradiol-17 beta.

OBJECTIVE

To determine the effectiveness and acceptability of personal hormone monitoring for contraception.

METHODS

A large prospective study was carried out on personal hormone monitoring for contraception when used with abstinence during the identified fertile days.

METHODS

Three country study under the auspices of the departments of Obstetrics and Gynaecology of the Universities of Birmingham, Dublin and Dusseldorf

METHODS

Seven hundred and ten women, median age 30, were recruited from the general population. They were required to have regular menstrual cycles (23-35 days) and to be delaying their next pregnancy.

METHODS

Personal hormone monitoring consists of a hand held monitor and disposable test sticks which measure changes in urinary concentrations of oestrone-3-glucuronide and luteinising hormone. An algorithm estimated the fertile days which were displayed by a red light.

RESULTS

One hundred and sixty two pregnancies occurred in 7209 cycles of use, of which 67 were method related pregnancies. The 13 cycle life-table method pregnancy rate (95 per cent CI) was 12. 1 per cent (9.3-14.8). The system allowed analysis of the effect of changes to the algorithm to modify the defined fertile period. As a result the algorithm was changed to increase the median warning of the luteinising hormone surge to six days. With the revised algorithm, half of the method pregnancies would have been prevented giving a calculated method pregnancy rate of 6.2 per cent (4.2-8.3) and method efficacy of 93.8 per cent. The continuation rate after 13 cycles was 78 per cent.

CONCLUSIONS

Personal hormone monitoring proved simple to use and will be of value to women who do not want to use other methods of contraception.