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Biomedical subjects

H H Goh

Publications and source records attributed to H H Goh.

At least 37 records · Page 2Linked to original sources

Simple office methods to predict ovulation: the clinical usefulness of a new urine luteinizing hormone kit compared to basal body temperature, cervical mucus and ultrasound.

A new urine luteinizing hormone (LH) kit, First Response (Tambrands Inc., Palmer, MA) was compared with basal body temperature (BBT), cervical mucus scoring and abdominal ultrasound follicular scanning in their ability to predict ovulation to within 2 days of the serum LH peak. BBT was kept daily. From day 10 daily ultrasound scanning and cervical mucus examination were performed and serum oestradiol, luteinizing hormone, follicular stimulating hormone and progesterone were assayed. First Response was significantly more accurate than BBT and cervical mucus when compared in their ability to predict ovulation to within 2 days of the LH peak (p less than 0.05). First Response pinpointed 93% (27/29) of the ovulatory cycles compared to 72% (18/25) and 61% (19/31) for BBT and cervical mucus respectively. It was better but not significantly so against abdominal ultrasound which predicted 77% (24/31). The implications of this finding and the value of the other simple office tests in clinical practice are discussed.

Ambulatory Care↗

Prolactin levels in menopausal women on long-term estrogen implants.

Prolactin levels were measured in 71 menopausal women before treatment and 32 treated with steroid implants. In neither group was there any case of hyperprolactinemia. Although prolactin levels were on average 13% higher in the women who had had long-term treatment with the implants, they were, nevertheless, not significantly different from the corresponding levels in the pretreated group. Treatment with steroid implants at the dose and duration studied therefore did not significantly increase the risk of hyperprolactinemia occurring in treated as compared with pretreated menopausal women.

Adult↗

The LH surge in humans: its mechanism and sex difference.

There is a sex difference in the response to an estrogen challenge test in humans, but, unlike with rats, this sex difference is not permanently imprinted in the central nervous system. Estrogen is not only the important ovarian signal to trigger off the LH surge, but it also probably plays an important role in activating the positive estrogen feedback mechanism in humans. For an LH surge to occur, amplification of the hypothalamic signal (enhanced secretion of GnRH) as well as sensitization of the pituitary responsiveness to GnRH are required. It is unlikely that androgens per se are responsible for suppressing the positive estrogen feedback in humans and the possible role of another gonadal factor other than androgens remains speculative. The LH surge is a neuroendocrine phenomenon involved primarily in the process of ovulation and it is not correlated to sexual identity and orientation. Furthermore, how the hypothalamic-pituitary axis (HPA) responds to the estrogen challenge can be accounted for purely by its exposure to a different steroid milieu without reference to gender identity or sexual orientation of the subject.

Estrogens↗

Contributions to reproductive medicine through in-vitro fertilization: a review.

In vitro fertilization (IVF) is now an accepted treatment procedure for subfertility. Its use has also contributed greatly to the understanding of our knowledge in reproductive medicine. This review looks at these contributions. In the female, IVF has made it possible to examine more closely ovarian physiology through the follicular micro-environment, follicular dominance and cohorts. In the male, the new sperm preparation technology has assisted the investigation of sperm parameters in-depth. A better understanding of human egg and sperm physiology, the fertilization process and pre-implantation phenomena has also contributed to better management of the infertile couple. Perhaps in the future, the pre-implantation embryo may be considered as a "patient".

Fertilization in Vitro↗

Follicular-phase response in two clomiphene-human menopausal gonadotropin regimes for an in vitro fertilization program.

Two clomiphene-human menopausal gonadotropin regimes were assessed for our in vitro fertilization and embryo replacement (IVF and ER) program since September 1983. Clomiphene, 50 mg bd, was taken from day 2 for 5 days. Human menopausal gonadotropin (hMG) was given from day 6; for the first regime, 75 IU/day was given for the first 3 days, and for the second, 150 IU/day. The subsequent dosages were dependent on the estradiol response. There were 9 cases for the first regime and 10 cases for the second. The mean number of hMG ampoules given was 16.5 and 19.25, respectively. The number of follicles seen on ultrasound was 3.0 +/- 0.5 and 3.4 +/- 1.2 (mean +/- SD), respectively. There was no statistical difference in the estradiol response up to the day of laparoscopic ova recovery for the two regimes. However, a spontaneous luteinizing hormone (LH) surge was observed in 4 of 9 cases in the first group and 6 of 10 cases in the second group. When a comparison was made between cases that had a spontaneous LH surge and cases that were given human chorionic gonadotropin (hCG), there was a higher estradiol level on the day of the laparoscopy in the hCG group with the lower hMG regime (P less than 0.05). There were no other differences. Our small series shows a 52.6% incidence of spontaneous LH surge with clomiphene-hMG. Hence such stimulated regimes can result in a high proportion of spontaneous LH surges; this may be an index of satisfactory endocrinological control in spite of an increase in the number of follicles.

Clomiphene↗

Effects of sex steroids on the positive estrogen feedback mechanism in intact women and castrate men.

We studied the effects of prolonged testosterone treatment on ovulatory function and positive estrogen feedback in women and of prolonged estrogen priming on gonadotropin feedback in castrate men. An estrogen provocation test was carried out in 4 groups of transsexual subjects: 12 female transsexuals in their early follicular phase (days 3-5; group 1A), 8 females who had been treated with Depo-testosterone (T) for 3-6 months (group 1B), 11 men who had been castrated 3 months previously (group 2A), and 4 male castrates treated with oral estrogen for 3 months starting 3 months after castration (group 2B). The estrogen provocation test consisted of 3 GnRH tests (100 micrograms) carried out immediately before (0 h) and 44 and 92 h after an im injection of estradiol valerate (10 mg). Responses to the estrogen provocation test in women with normal menstrual cycles (group 1A) were typically female. After initial suppression at 44 h, a LH surge (positive feedback) occurred at 92 h. Pituitary responsiveness, however, was amplified both at 44 and 92 h. Prolonged T priming of women in group 1B did not inhibit the estrogen-induced LH surge, nor was the amplitude of the surge blunted. Removal of androgens and other testicular factors (group 2A) did not result in the appearance of an estrogen-induced LH surge. On the other hand, prolonged estrogen priming in male castrates (group 2B) resulted in activation of the positive feedback mechanism; a LH surge in response to the estrogen provocation occurred. The results of the present study imply that 1) contrary to an earlier suggestion, testosterone does not block or blunt the LH surge, indicating that it is probably not responsible for suppressing the LH surge in normal men; 2) testosterone can cause ovulatory failure without suppressing the LH surge in women; and 3) prolonged estrogen priming may be involved in activation of the positive feedback mechanism in humans.

Adult↗

The feminisation of gonadotrophin responses in intact male transsexuals.

In castrated animals and hypogonadal men other workers have shown an LH surge following oestrogen administration similar to that found in the normal female. However, there is no evidence that this can be achieved in intact males. We have therefore studied male transsexual patients before and after chronic oestrogen therapy given for at least three months to feminise the body habitus before undergoing plastic surgery. Subjects were assessed for the acute effects of oestradiol valerate on sex steroid hormone levels and gonadotrophin responses to gonadotrophin releasing hormone. The results showed that longterm treatment could transform the normal male pattern of a suppressive effect of oestrogen on gonadotrophin release to one where the oestrogen increased LH levels and amplified the effect of LHRH on gonadotrophin release. This pattern is similar to that found in normal women and indicates that longterm oestrogen treatment to males can feminise gonadotrophin responses.

Adult↗

Cord plasma alpha-fetoprotein values and neonatal jaundice.

Umbilical cord plasma alpha-fetoprotein (AFP) values were determined in 127 infants with hyperbilirubinemia (56 glucose-6-phosphate dehydrogenase (G-6-PD) deficient and 71 G-6-PD normal) and 136 control subjects (73 G-6-PD deficient and 63 G-6-PD normal). The mean alpha-fetoprotein value of 173 +/- 35.2 (SD) mg/L for the group of infants with hyperbilirubinemia was significantly greater than that (122 +/- 21.7 mg/L) for the control infants (P less than .001). G-6-PD status and sex did not significantly affect the alpha-fetoprotein values. Using an alpha-fetoprotein level of 130 mg/L as a "cut-off" value, the incidence of false-positive results was 25.5% and the incidence of false-negative results was 11.8%. This test can be used as a screening procedure to detect infants at high risk for hyperbilirubinemia.

China↗

Control of gonadotrophin secretion by steroid hormones in male castrates: site of oestradiol action.

Four normal healthy castrated male transsexuals who were not on hormone therapy for at least 4 months volunteered for this study. Each subject received 3 infusions at weekly intervals--the first consisting of LHRH alone, the second of LHRH and oestradiol and the third of oestradiol alone. Venous blood samples were collected at 20-minute intervals 1 hour before the start and during the whole period of infusion. Plasma concentrations of FSH, LH and oestradiol were measured by radio-immunoassay. On an average, 100 micrograms of LHRH enhanced the area under the LH secretion curve by 177% and under the FSH curve by 68%. Oestradiol had a differential effect on the endogenous secretion of LH and FSH, suppressing them by 53% and 18%, respectively. Similarly, the LHRH-stimulated release of LH was significantly inhibited to a greater extent (42%) than that of FSH (23%, P less than 0.05; paired t test). Such an observation and in the light of our acceptance of the single releasing hormone theory, suggests that the differential actions of oestradiol on the secretions of FSH and LH are due to mechanisms residing in the pituitary.

Castration↗

Plasma oestriol in pregnancies complicated by diabetes mellitus.

We studied the plasma oestriol concentration during increasing gestation in 192 normal pregnancies and 96 pregnancies complicated by diabetes mellitus. Among the 96 patients there were 16 established, 32 gestational, 29 'persistent' gestational and 19 either gestational or 'persistent' gestational diabetic pregnancies. Serial blood samples were collected and their concentrations of oestriol (total oestriol) determined by radioimmunoassay. The distribution of birthweights and placental weights around each gestational period was skewed to the right. Therefore, the 5th and 95th percentiles were obtained after computing a logarithmic transformation of the data. The incidence of big and small babies in all diabetic groups, except that in the gestational diabetic group, was significantly higher than that in the group of normal pregnant women. The distribution of oestriol concentrations was also skewed to the right and had to be normalized by logarithmic transformation. The oestriol profile in normal pregnancies had a wide scatter, especially after the 37th week. Serial measurements with reference to the normal oestriol profile showed a detection rate of approximately 85% for both normal and abnormal foetal outcome. There were 15% of false negative and 16% of false positive results. Results in this study indicate that serial blood oestriol measurement may be a useful additional index for foetal monitoring in pregnancies in diabetic women. Furthermore, if large scale screenings using a single estimation are performed, it is best carried out between the 33rd and 34th week of gestation.

Birth Weight↗

Steroidogenesis in hydatidiform mole--sources of androgens.

Plasma concentration of testosterone is significantly higher in patients with a molar pregnancy than in those with a normal pregnancy at similar gestation. The source of this raised level of testosterone has been controversial with some suggesting the molar trophoblast while others, the hyperstimulated ovary as the main contributor. We have carried out a series of investigations involving measurements of testosterone levels in plasma before and after evacuation of the uterus and in fluid from molar vesicle and lutein cyst. Furthermore, in vitro study on the conversion of androstenedione and dehydroepiandrosterone (DHEA) to testosterone and in vivo conversion of DHEA to testosterone and oestradiol before and after evacuation of the mole were conducted. Considering all the evidence together, it appears that the hyperstimulated ovary is probably the major source of the raised concentration of testosterone in molar pregnancy. On the other hand, although the molar trophoblast also makes some contribution as in normal pregnancy, the molar trophoblast is essential for the production of oestrogens.

Dehydroepiandrosterone↗

Research and development in obstetrics & gynaecology in the Department of Obstetrics & Gynaecology at the National University of Singapore.

This is a review of the research and achievements of the Department of Obstetrics and Gynaecology, National University of Singapore since 1949. The research activities reviewed are Fertility Control, Subfertility, Reproductive Endocrinology, In-Vitro Fertilization, Trophoblastic Disease, Prostaglandins and Perinatal Medicine. The University Department has kept abreast with the Singapore norm of two-child families by providing the most sophisticated technology and expertise. The perinatal mortality and stillbirth rates have been reduced to 11 and 6 per thousand births. Prostaglandin research in the Department includes an investigation of the involvement of these substances in various physiological processes, pharmacological studies with different prostaglandins and development of clinical applications. Between 1974 and 1981 we had studied 12 intrauterine contraceptive devices, both on a departmental basis and in conjunction with international agencies. The newer medicated devices have proved to offer significant advantages over the original inert plastic configuration. Metabolic changes in Singapore women on the oral pill and injection Depoprovera were studied. Impaired glucose tolerance and raised fasting total lipids were found in women on the pill. Marginal changes in carbohydrate metabolism only were found in women on injection Depoprovera. Hypercoagulation changes in the blood occurring in Singapore women varied with the dose of the synthetic or natural oestrogen medication. Initially, the fibrinolytic activity was enough to compensate for these changes; however after two years there were signs of decompensation. Progestogens affect coagulation via their influence on the liver functions. Hypercoagulation changes also occurred in pregnancy and was of a greater magnitude than oestrogen or progestogen medication. In many obstetric disorders, including hydatidiform mole, there was evidence of intravascular coagulation. The introduction of endocrine function tests has greatly improved patient care in our Department, in particular those related to endocrine disorders. Application of the immunoassays to basic research has shown that physiological levels of oestradiol exert a negative feedback effect on both FSH and LH secretions in men. The greater suppression of LH than of FSH secretion by pharmacological doses of estradiol is possibly due to different control mechanisms in the pituitary for the synthesis and release of both gonadotrophins. Physiological level of testosterone per se has a definite negative feedback effect on the secretion of LH but not on FSH. Pharmacological doses of the 5-alpha-reduced metabolites of testosterone have been shown to suppress both LH and FSH indicating that some of the actions of testosterone could be medicated by these metabolites of which the 3 alpha-androstanediol and 3 beta-androstanediol are the more likely candidates.

Academic Medical Centers↗

Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. II. Effects of androgens alone and in combination with oestradiol on the secretions of FSH and LH.

Twenty-nine infusions in twenty castrated male transsexual volunteers were carried out over a period of 7 h with subjects lying in the supine position. The effects of different doses of testosterone and its 5 alpha-reduced metabolites as well as the effect of testosterone in combination with oestradiol on gonadotrophin secretion were evaluated. Different and varying degrees of suppression of plasma levels of FSH and LH were observed. The infusions of 2.4 mg testosterone, 5 alpha-androstan-3 alpha-17 beta-diol (3 alpha-diol), 5 alpha-androstan-3 beta-17 beta-diol (3 beta-diol) but not dihydrotestosterone (DHT) caused significant suppression of LH. FSH, on the other hand was not significantly inhibited by the androgens at this rate. At higher doses all four androgens suppressed LH secretion significantly. FSH was similarly suppressed by the androgens except by DHT. A differential effect on FSH and LH secretions was noted with the combined regime of testosterone and oestradiol. The combined regime did not cause a significantly higher degree of FSH suppression compared with either 200 microgram of oestradiol or 12 mg of testosterone infused alone. The level of LH, however, was suppressed to a greater extent than either of the hormones when given alone. The inhibitory effect of testosterone demonstrated in this study could be due to the parent hormone or its 5 alpha-reduced metabolites. Pharmacological doses of testosterone could exert a greater degree of LH suppression through its conversion to oestradiol. It is likely that oestradiol and testosterone act on gonadotrophin secretion through different mechanisms and that they have an additive suppressive effect on the secretion of LH but not FSH. The potencies for the androgens to suppress gonadotrophin secretion can be ranked as: 3 alpha-diol = 3 beta-diol greater than testosterone greater than dihydrotestosterone.

Androgens↗

Recovery of hypophyseal-testicular function from sex steroid treatment and the pituitary response to castration in male transsexuals.

Twenty-one male transsexuals who had been on steroid hormone therapy for at least 1 year volunteered for this investigation. Their hormone profiles after stopping sex steroid hormone treatment for periods ranging from 2 to 70 days were examined. Based on their testosterone levels before the sex-reassignment operation which includes castration, penectomy and the construction of an artificial vagina, two separate groups can be distinguished; those with low (group A) and the other with normal (group B) levels. The gonadotrophins levels in group A and group B were (respectively) significantly (P less than 0.05) lower and higher than corresponding levels in a group of normal males. Castration had caused elevations of FSH and LH in both groups. Although the increment rates were different, both groups attained the same maximum levels of FSH and LH. Within each group, the patterns of FSH and LH responses to castration were similar. However, differences in rates and time of significant elevation of FSH and LH were noted. These observations indicate that there is a delay between the cessation of steroid treatment and the recovery of testicular and hypophyseal functions. Testicular function seems to be altered by steroid treatment since excessive secretions of FSH and LH are needed to produce normal testosterone levels. The secretions of FSH and LH are controlled in some ways by the same mechanisms, while they, in other respects, are controlled by different factors.

Castration↗

Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. I. Effects of oestradiol infusion on plasma levels of follicle-stimulating hormone and luteinizing hormone.

Twenty-four infusions of oestradiol (E2) in graded doses ranging from 0--200 micrograms administered over a period of 7 hours were carried out in eleven healthy male transsexuals who had undergone sex reassignment at least 3 months previously. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were analysed by radioimmunoassay, while sex hormone binding globulin (SHBG) was measured using 3H-testosterone as the saturating ligand. Infusion of 5--200 micrograms of E2 raised plasma E2 to levels ranging from 38.4--367.8 pg/ml which present 83%--800% of levels found in a control group of sixty-three normal males. SHBG capacity remained unchanged at all doses of E2 studied. No change in plasma levels of FSH and LH was observed in control infusions and infusion of 5 micrograms of E2. From 10 micrograms-200 micrograms, suppression of plasma levels of FSH was noted at the 5--7 hour period. The suppression increased up to 20 micrograms and thereafter the levels of FSH remained constant. On the other hand, the suppression of LH increased up to the highest E2 dose (200 micrograms) studied. Further, significant suppression of LH occurred earlier than the 5--7 hours as the dose of E2 increased. These observations are consistent with the conclusions that: (1) E2 plays a part in the regulation of secretion of FSH and LH in men; and (2) at doses higher than physiological, E2 exerts a differential effect on the secretion of FSH and LH.

Castration↗