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Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 199 records · Page 11Linked to original sources

Ultrasound assessment of changes in the ovary and the uterus during LHRH therapy.

Twenty-seven women with secondary amenorrhoea have been treated with pulsatile subcutaneous luteinising hormone releasing hormone (LHRH). Serial ultrasonic observations of increasing follicular diameters and changes in the size of the uterus have been recorded. The rate of the increase of the diameter of dominant follicles in LHRH induced cycles is identical to that observed in women undergoing spontaneous cycles. An interesting correlation was observed between follicular diameter and uterine size. The correlation suggests that uterine size measured ultrasonically can be used as a bio-assay of follicular oestradiol production. Uterine growth continues throughout the luteal phase of conception cycles and can be used as a very early sign of pregnancy.

Adult↗

Infertility, megalocystic and polycystic ovaries: differential response to LHRH therapy.

A group of anovulatory women have been identified as being particularly difficult to treat with pulsatile luteinising hormone releasing hormone (LHRH). Further investigation shows that sub-division into two groups is possible on the basis of ovarian morphology on ultrasound imaging. Ovulation can be successfully induced in women with megalocystic ovaries and 14 of those women treated conceived.

Adult↗

A new generation of pulsatile infusion devices.

A selection of pulsatile infusion devices suitable for administering LHRH are described. The principles of operation and control options of the different pumps are explained, including the new compact direct-drive syringe pump. The relative merits of these infusion systems are discussed and it is concluded that size, ease of use and range of application are paramount.

Gonadotropin-Releasing Hormone↗

Inhibition of 3-beta-hydroxy steroid dehydrogenase activity in first trimester human pregnancy with trilostane and WIN 32729.

The effects of equivalent doses of two inhibitors of the 3-beta-hydroxy steroid dehydrogenase enzyme system--WIN 24540 (trilostane) and WIN 32729--on the secretion of progesterone in early human pregnancy are described. Patients and controls less than 12 weeks pregnant were given a single dose of either drug and the resultant hormonal changes monitored for 7 1/2 h. A consistent fall in plasma progesterone concentrations occurred at all doses and, at the highest dose, they fell to less than 50% of pre-treatment levels. However, whilst with trilostane the associated increase in plasma concentrations of pregnenolone was always accompanied by a rise in plasma DHA concentrations, with WIN 32729 there appeared to be no adrenal effect at the lower dosage levels. These data demonstrate inhibition of progesterone secretion in human pregnancy using non-hormonally active steroids. The pattern of steroid precursors indicates that while both drugs inhibit 3-beta-hydroxy steroid dehydrogenase activity, WIN 32729 is more selective and only interferes with adrenal steroid biosynthesis at high doses.

3-Hydroxysteroid Dehydrogenases↗

Plasma and salivary androstenedione and dihydrotestosterone in women with hyperandrogenism.

Sensitive radioimmunoassays (RIA) have been developed to measure salivary and plasma androstenedione and dihydrotestosterone levels in normal women, women with polycystic ovaries (PCO) and idiopathic hirsutism, and patients on antiandrogen therapy. There was a highly significant correlation (r = 0.92, P less than 0.001) between the concentration of androstenedione in saliva and the unbound concentration in plasma. The unbound plasma androstenedione was measured in the dialysate by RIA and ranged from 6.0-10.4% of the total concentration. Salivary and plasma androstenedione levels in patients with PCO (185 +/- 72 pg/ml (n = 11) and 3262 +/- 814 pg/ml (n = 12) respectively) and in those with hirsutism (151 +/- 110 pg/ml (n = 25) and 2177 +/- 1096 pg/ml (n = 25) were significantly higher than levels in normal women (78 +/- 30 pg/ml (n = 18) and 787 +/- 355 pg/ml (n = 18). A good correlation (r = 0.82, P less than 0.001) was also found between salivary and unbound plasma dihydrotestosterone concentrations. Salivary and plasma dihydrotestosterone levels in patients with PCO (8.2 +/- 3.3 pg/ml (n = 9) and 167 +/- 45 pg/ml (n = 11) respectively and hirsutism (6.0 +/- 2.1 pg/ml (n = 14) and 176 +/- 69 pg/ml (n = 17) were significantly higher than levels in normal women (4.5 +/- 1.3 pg/ml (n = 17) and 90 +/- 44 pg/ml (n = 16), although there was a large overlap between groups. A similar decrease was observed in salivary and plasma androstenedione levels after treatment with cyproterone acetate (CA) and ethinyl oestradiol (EE) for 3 months. Plasma dihydrotestosterone levels remained elevated in 47% of treated women whereas only 21% of cases had raised salivary dihydrotestosterone levels. It is concluded that, as with testosterone salivary androstenedione and dihydrotestosterone measurements give a good reflection of their biologically active levels in normal, hyperandrogenic and CA + EE treated women.

Adolescent↗

Salivary testosterone: relationship to unbound plasma testosterone in normal and hyperandrogenic women.

A sensitive radioimmunoassay (RIA) was used to measure salivary testosterone levels in normal women, in patients with polycystic ovaries (PCO), and in women with hirsutism. There was a highly significant correlation (r = 0.79, P less than 0.001) between the concentration of testosterone in saliva [12.3 +/- 7.8 (SD) pg/ml] and the concentration of unbound testosterone in plasma (5.2 +/- 3.1 pg/ml) in matched samples collected from 56 women including normals, patients with clinical signs of hyperandrogenism, and women treated with a combination of cyproterone acetate (CA) and ethinyl oestradiol (EE). The unbound plasma testosterone was measured in the dialysate directly using a sensitive RIA. Salivary and plasma testosterone levels in patients with PCO (20.6 +/- 8.5 and 626 +/- 187 pg/ml respectively, n = 14) and in those with hirsutism (13.9 +/- 5.6 and 421 +/- 170 pg/ml, n = 30) were significantly higher (P less than 0.001) than levels in normal women (7.7 +/- 2.6 and 196 +/- 68 pg/ml, n = 36). Treatment for 3 months with CA and EE resulted in a decrease (mean 68%) in salivary testosterone levels in all patients studied (n = 15), but the suppression of plasma testosterone (mean 34%) was not observed in all cases. It is concluded that measurement of salivary testosterone gives a useful indication of levels of biologically available androgen in hyperandrogenic women, before and during CA/EE therapy.

Adolescent↗

Failure of FSH to influence aromatization in human adipose tissue.

Since gonadotrophins are known to influence aromatase activity in gonadal tissue, an attempt was made to correlate serum gonadotrophin concentrations with the activity of aromatase enzyme in adipose tissue. No relationship between in-vitro measurements of adipose tissue aromatase activity and FSH or LH levels in serum was found. Four of five women studied with premature ovarian failure had low levels of aromatase activity despite having postmenopausal levels of serum gonadotrophins. In addition, FSH receptors could not be demonstrated on while adipose tissue, isolated fat cells or stromal vascular tissue.

Adipose Tissue↗

Normal fertility in women with post-pill amenorrhoea.

After exclusion of primary ovarian failure and causes of infertility not due to contraception 48 patients with post-pill amenorrhoea (PPA) and 47 patients whose amenorrhoea did not follow oral contraception received treatment aimed at inducing ovulation. In the patients with PPA the cumulative conception rate was 91% at 12 months from the start of treatment and 98% at 24 months. 80% gave birth to a child by 18 months and 95% by 30 months. These rates were similar to those of the non-PPA group and to previously published normal rates. Hence PPA poses no serious threat to fertility, unlike the tubal damage that may result from use of an intrauterine device. Whatever their previous menstrual history women, especially the nulliparous, who are concerned about their future fertility should be recommended oral contraception in preference to an intrauterine device.

Amenorrhea↗

Post-pill amenorrhea: a causal study.

The distribution of distinguishable disorders in 102 patients with post-pill amenorrhea has been compared with that in 166 other patients with secondary amenorrhea, including 123 patients who had never used oral conception. In the post-pill group there was a 13% to 21% excess of patients who had a functional disorder without any weight loss or psychological disturbance to account for it and who typically were estrogenized and demonstrated intact feedback systems by their ovulatory response to clomiphene (the so-called cycle initiation defect). This excess might be explained by biased selection of oral contraception, but it seems wiser to assume a causal relationship, which amounts to a true risk of post-pill amenorrhea in less than 1 per 1000 users. No risk was revealed of primary ovarian failure, hyperprolactinemia, or pituitary tumor.

Adolescent↗

Failure of 2-hydroxyoestrone to lower prolactin concentrations in hyperprolactinaemic women.

The catechol oestrogen 2-hydroxyoestrone has been reported to lower serum prolactin concentrations acutely in normal women and it has been proposed that it may be effective in suppressing prolactin secretion in hyperprolactinaemic patients. Five women with hyperprolactinaemia and anovulation were studied. Following a control infusion, 2-hydroxyoestrone was given at a rate of 80 micrograms/h for 4 h. In no patient was there a fall in prolactin levels and no changes were observed in gonadotrophin concentrations. We conclude that a short-term infusion of 2-hydroxyoestrone, at a dose which will produce high blood levels of the steroid, does not affect prolactin or gonadotrophin secretion in hyperprolactinaemic states.

Adult↗

Climacteric flushing: clinical and endocrine response to infusion of naloxone.

Six postmenopausal women with frequent attacks of flushing were studied by measuring plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin and noradrenaline concentrations at regular and frequent intervals and at the time of each of 82 flushes. The hormone measurements were made on a control day and on the second day during infusion of either naloxone (22 micrograms/min) or saline. The perception of a flush was associated with a significant increase of plasma LH concentrations. There were no significant changes in plasma FSH, prolactin or noradrenaline concentrations. Naloxone infusion resulted in a highly significant reduction in the frequency of flushes and in the number of LH pulses. We conclude that flushing and its neuro-endocrine correlates are related to activation of opiate receptors. Naloxone may provide the basis for a non-steroidal treatment of climacteric flushing attacks.

Adult↗