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Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 181 records · Page 10Linked to original sources

The investigation of female gonadal dysfunction.

An approach to the investigation of ovarian dysfunction has been presented here with a particular emphasis on the importance of effective imaging of the ovary and uterus by ultrasonography. Essential endocrine investigations in the various clinical manifestations of altered ovarian function have been placed in the context of recent research on the control of female reproduction.

Adult↗

Gonadotrophin control of follicular development.

In order to investigate the endocrine requirements for induction of follicle maturation, ovulation and luteal function we have measured plasma LH and FSH concentrations in 109 cycles induced by treatment with LHRH in 25 women with amenorrhoea of diverse aetiology. The major clinical and endocrine subgroupings were polycystic ovarian disease (PCO), Kallmann's syndrome, weight related amenorrhoea and hyperprolactinaemia. By analysis of variance of the LH and FSH concentrations obtained three times per week in the follicular phase in 77 ovulatory cycles (including 24 conception cycles), we found that in women with PCO the mean LH concentration was 19.5 IU/l. In hyperprolactinaemia and secondary amenorrhoea of non-specific aetiology the mean LH concentration was 11.6 IU/l and in patients with hypogonadotrophic hypogonadism and weight-related amenorrhoea it was 7.2IU/l. These mean LH concentrations were significantly different from each other (P less than 0.001). We speculate that the high LH concentrations in the follicular phase may impair the final stages of oocyte maturation and so contribute to the infertility of these patients. FSH concentrations in the follicular phase were lower in patients with hypogonadotrophic hypogonadism and weight-related amenorrhoea than in other groups. Although the differences were statistically significant (P less than 0.001) the difference was small (mean FSH in hypogonadotrophic hypogonadism and weight-related amenorrhoea 4.3 IU/l vs 6.3 IU/l in the others) and of uncertain biological significance. During the luteal phase, no differences between any of the groups in LH and FSH concentrations were found.

Adult↗

Ultrasound demonstration of increased frequency of functional ovarian cysts in women using progestogen-only oral contraception.

Asymptomatic volunteer women with a regular pattern of uterine bleeding and using the progestogen-only oral contraceptive pill were compared with control women who were not exposed to hormones. Pelvic ultrasound scanning at the end of the next bleeding episode after recruitment demonstrated functional cysts with maximum diameters ranging between 30 and 58 mm in eight of the 21 pill users, four of whom also had palpable ovaries, three cysts regressed during the next cycle. Of the 13 women with normal ovaries initially, four developed a new functional cyst of which two were associated with pain. Of the 12 women with cysts seven complained of pain at some time during the monitored cycle. Among 21 control women only one symptom-free (42 mm) cyst was shown on the initial postmenstrual ultrasound scan and this resolved painlessly during the scanned cycle with ovulation from the opposite ovary. Ovulation was also demonstrated in 16 of the remainder; but in none of the three control women who developed asymptomatic functional cysts (35-47 mm in size) while under observation. Since 11 of the 14 pill-users who failed to ovulate also had a functional cyst, the contraceptive efficacy may depend in part on this association. Pain symptoms may make the method less acceptable and give rise to diagnostic problems and inappropriate therapies.

Adult↗

Ovarian ultrasound assessment in normal children, idiopathic precocious puberty, and during low dose pulsatile gonadotrophin releasing hormone treatment of hypogonadotrophic hypogonadism.

Ultrasound assessment of ovarian volume, follicular size, and uterine growth was undertaken in 40 normal premenarcheal girls aged 6 months to 14 years. Ovarian follicles were detected from 6 months of age and increased in size and number, so that after the age of 8.5 years there was a progressive increase in the incidence of 'megalocystic' appearance. Eight girls with idiopathic precocious puberty had large megalocystic ovaries which regressed on treatment with gonadotrophin releasing hormone analogue. These findings contrasted with those seen in two prepubertal patients with hypogonadotrophic hypogonadism in whom the natural sequence of ovarian development was greatly accelerated by pulsatile administration of native gonadotrophin releasing hormone.

Adolescent↗

Problems in the use of pulsatile gonadotrophin-releasing hormone for the induction of puberty.

The induction of puberty by the administration of subcutaneous 15-micrograms pulses of gonadotrophin-releasing hormone (GnRH) every 90 min during day and night is described in two patients. Too rapid an induction of puberty occurred in one patient while initial progress in the other ceased after the development of pituitary desensitisation. We have attributed these results to the use of GnRH pulses in too high amplitude, and we suggest a more appropriate dose regimen.

Adolescent↗

A miniature infuser for the pulsatile administration of LHRH.

This paper describes a compact, battery-powered infuser that is light, unobtrusive and simple to operate. A novel direct-drive method is used to deliver intermittent boluses of hormone at predetermined time intervals via a special prefilled syringe. Normal pregnancy rates were achieved in anovulatory women when infused with luteinising hormone releasing hormone (LHRH).

Biomedical Engineering↗

The effects of cyproterone acetate and ethinyl oestradiol on carbohydrate metabolism.

Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as anti-androgen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and women were studied in two groups: the first when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13 to 22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to intravenous tolbutamide was increased by 50% but there was no accompanying change in the glucose nadir as compared with controls. These results show that the combination of CA and EO causes insulin resistance. Plasma C-peptide concentrations following oral glucose were unchanged compared with controls. This shows that the observed hyperinsulinaemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. We propose that these effects are due to a CA-induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C-peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide but this was not significant. We conclude that these results are explained by a reduced but persisting effect of CA.

Acne Vulgaris↗

The treatment of hypogonadotrophic hypogonadism in men by the pulsatile infusion of luteinising hormone-releasing hormone.

The effects of chronic subcutaneous infusion of luteinising hormone-releasing hormone (LHRH) have been studied in a group of 17 male patients with hypogonadotrophic hypogonadism (HH). Ten of the patients had primary and seven secondary failure of gonadotrophin release, and all but four had previously been treated with gonadotrophin injections. Treatment was continued for between one and 18 months and was well tolerated by all except one patient who became allergic to LHRH. An increase in the basal gonadotrophin concentrations occurred in all except four patients within one week of the initiation of therapy, and this was associated with a rise in the serum testosterone level in eight patients. Increased spermatogenesis was demonstrated in seven cases and three pregnancies have resulted thus far. Pituitary desensitisation to the effects of LHRH was found in five subjects with primary HH who failed to produce any increase in testosterone secretion despite an initial stimulation of gonadotrophin release. We conclude that chronic pulsatile infusion of LHRH is an effective technique for the treatment of some cases of hypogonadotrophic hypogonadism.

Adult↗

Hypothalamic hypopituitarism in a patient with a basal encephalocoele--treatment with luteinizing hormone-releasing hormone.

A 20-year-old patient presented with primary amenorrhoea and growth hormone deficiency caused by a basal encephalocoele. She was found to have developed diabetes insipidus in the 8 years following diagnosis. Gonadotrophin release in response to bolus injection of luteinizing hormone-releasing hormone (LHRH) was normal, as was thyrotrophin and adrenocorticotrophin (ACTH) secretion. Pulsatile administration of LHRH by the subcutaneous route resulted in normal ovulation and subsequent menstruation. The investigation and management of patients with basal encephalocoeles are discussed in the light of these findings.

Adult↗

The role of subcutaneous luteinising hormone releasing hormone in the induction of ovulation.

Induction of ovulation using pulsatile luteinising hormone releasing hormone (LHRH) has been performed in 53 anovulatory women who had previously failed to respond to clomiphene. Pelvic ultrasound imaging prior to treatment provided an accurate means of predicting the subsequent response to subcutaneous and intravenous therapy and was of particular value in differentiating patients with ovarian enlargement due to multiple intraovarian follicles. Subcutaneous administration was appropriate in the majority of patients. Thirty-eight conceptions have been confirmed.

Adult↗