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D T Baird

Publications and source records attributed to D T Baird.

At least 55 records · Page 3Linked to original sources
PubMed2001

Is there a place for different isoforms of FSH in clinical medicine? IV. The clinician's point of view.

Follicle stimulating hormone (FSH) plays an important role in gametogenesis in both men and women. In men it is required for the establishment and probably maintenance of spermatogenesis. In women it stimulates the growth of ovarian follicles and fluctuations in its secretion are involved in the selection of the ovulatory follicle. It is now possible by recombinant DNA technology to synthesize a range of isoforms of FSH with differing biological action and half-life which would provide a greater degree of flexibility in the treatment of women with anovulatory infertility. Longer acting isoforms of FSH would find clinical application in the treatment of hypogonadotrophic men.

Female↗
PubMed2001

Progesterone antagonists increase androgen receptor expression in the rhesus macaque and human endometrium.

Antiprogestins (APs) inhibit estradiol (E(2))-stimulated endometrial growth in women and nonhuman primates, but the mechanism of this "antiestrogenic" action is unknown. Here, we report that APs up-regulate endometrial androgen receptor (AR) in both women and macaques, an effect that might play a role in the antiproliferative effects of APs on the primate endometrium. In addition, because there are discrepancies in the literature on the regulation and localization of AR in the primate endometrium, we used both in situ hybridization and immunocytochemistry to evaluate hormonal influences on endometrial AR in women and macaques. In ovariectomized macaques, the following treatments were given for 4 weeks each: E(2) alone, E(2) + progesterone (P), E(2) + mifepristone (RU 486), and E(2) + P + RU 486. In women, samples were obtained during the normal menstrual cycle and after treatment with either RU 486 for 30 days at 2 mg/day, or after a single oral administration of 200 mg RU 486 on cycle day LH + 2. In macaques, E(2) significantly increased AR expression above vehicle controls; E(2) + RU 486 increased binding further; E(2) + P decreased AR binding; and E(2) + P + RU 486 treatment caused an intermediate elevation in AR binding. In macaques treated with E(2) alone, stromal AR staining was predominant, and P treatment suppressed that staining. E(2) + RU 486 or E(2) + P + RU 486 treatment produced a striking up-regulation of glandular epithelial AR staining and enhanced the stromal AR signal. In situ hybridization analyses confirmed the immunocytochemistry data. Similar induction of glandular AR staining and enhanced stromal AR staining were obtained in macaques treated with ZK 137 316 and ZK 230 211. During the natural cycle in women, stromal AR staining predominated and was greater in the proliferative than the late secretory phase. RU 486 treatment of women up-regulated glandular epithelial AR staining after either daily treatment for 30 days with 2 mg/day or after a single oral dose of 200 mg. In summary, endometrial AR was highest in the stroma during the human proliferative phase (or during E(2) treatment in macaques) and lowest during the late secretory phase in women (or after E(2) + P treatment in macaques). In both species, RU 486 induced AR expression in the glands and enhanced AR expression in stromal cells. Because androgens can antagonize E(2) action, enhanced endometrial AR expression induced by APs could play a role in the antiproliferative, "antiestrogenic" effects of APs in primates.

Animals↗
PubMed2001

Inhibin A is a follicle stimulating hormone-responsive marker of granulosa cell differentiation, which has both autocrine and paracrine actions in sheep.

The aim of these studies was to examine the origin, control and local actions of inhibin A in monovular species, using the sheep as a model. Experiment 1 examined the pattern of mRNA expression for the inhibin subunits in relation to follicular size and pattern of expression to other differentiative markers in granulosa (P450 aromatase) and thecal cells (P450 17alpha-hydroxylase). Experiment 2 examined the pattern of inhibin A production, in relation to oestradiol, by granulosa cells induced to differentiate in vitro with follicle-stimulating hormone (FSH). Experiment 3 examined possible paracrine and autocrine actions of inhibin A by determining the effect of addition of human recombinant inhibin A and/or antiserum to inhibin on gonadotrophin-stimulated cellular differentiation. The results of Experiment 1 showed that expression of mRNA encoding inhibin subnuits alpha, beta(A) and beta(B) is greater (P<0.05) in large oestrogenic follicles than in small follicles but that only expression of the inhibin beta(A) subunit differs (P<0.05) between large oestrogenic and non-oestrogenic follicles. Expression of 17alpha-hydroxylase, but not of the luteinising hormone (LH) receptor, in thecal cells was related to both the size and the oestrogenicity of antral follicles, in a manner similar to that of the inhibin subunits. Experiment 2 demonstrated that the production of inhibin A by sheep granulosa cells is FSH-responsive after prolonged exposure (P<0.001) and precedes the production of oestradiol by around 48 h in the differentiative cascade induced in granulosa cells by FSH. The results of Experiment 3 showed that inhibin A can augment gonadotrophin-stimulated steroid production by both granulosa and theca cells (P<0.01), and that the addition of antiserum to inhibin can inhibit FSH-stimulated oestradiol production by granulosa cells from both small and large follicles (P<0.001). We conclude that inhibin A is an FSH-responsive marker of granulosa cell differentiation which has both autocrine and paracrine actions in sheep.

Androstenedione↗
PubMed2001

The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene.

Genetic variations in ovulation rate which occur in different breeds of sheep provide useful models to explore the mechanisms regulating the development of antral follicles. The Booroola gene, an autosomal mutation that affects ovulation rate, has been known for over two decades and despite intensive research it has not yet been identified. Using resources from human genome mapping and known data about gene linkage and chromosome location in the sheep, we selected the gene encoding the Bone Morphogenetic Protein receptor (BMPR) type 1 B (ALK-6) as a candidate site for the mutation. The BMPR1B gene in the human is located at the region linked with the Booroola mutation, syntenic to chromosome 6 in the sheep. A fragment of the sheep BMPR1B gene was cloned from an ovarian cDNA and the deduced aminoacid (AA) sequence is over 98% homologous to the known mammalian sequences. cDNA and genomic DNA from 20 Booroola genotypes were screened and two point mutation were found in the kinase domain of the receptor, one at base 746 of the coding region (A in the ++ to a G in FF animals) which results in a change from a glutamine in the wild type to a arginine in the Booroola animals. Another point mutation was identified at position 1113, (C to A) but this mutation does not change the coding aminoacid. The first mutation was confirmed in genomic DNA from 10 ewes from an independent Brazilian flock which segregates the Booroola phenotype. In all instances homozygous FecB gene carrier (n=11) had only the 746 A to G mutation, non gene carriers (n=14) had only the wild type sequence and heterozygote gene carriers (n=5) had both sequences. This mutation in the subdomain 3 of the kinase domain could result in an alteration in the expression and/or phosphorylation of SMADs, resulting in the phenotype characteristic of the Booroola animals which is the 'precocious' development of a large number of small antral follicles resulting in increased ovulation rate.

Amino Acid Sequence↗
PubMed2000

Ovarian autografts in sheep as a model for studying folliculogenesis.

The studies outlined in this review indicate that the cortical autograft, in addition to its clinical application as a means to restore fertility, represents a valuable experimental model that can be exploited to examine aspects of both early and terminal follicle development. The autograft procedure is a means to experimentally deplete the follicle population in an individual and this procedure results in similar endocrine changes and reproductive cycle perturbances as those observed in aged sheep and women with incipient ovarian failure. This methodology therefore represents a non-primate large animal model to study the consequences of, and possible interventions to overcome, reproductive problems associated with depleted ovarian follicular reserves. Without the necessity of keeping animals for large periods of time so that this depletion can occur naturally. In terms of early follicle development, the fact that the ischaemia that occurs during revascularisation of the autograft effectively synchronises follicle development at the primordial stages of development means that the autograft can be used as a model to study the control of early follicle development. This model has been used to examine the role of FSH (follicle stimulating hormone) in the control of early follicle development and the preliminary data presented provides strong evidence that FSH does indeed modulate early folliculogenesis, confirming the value of this model as a means of performing experimental investigations in this area. Further work using this model will concentrate on the role of other endocrine and local factors in the control of early folliculogenesis and the identification of the key developmental checkpoints during this process, with a view to designing physiological culture systems to support early follicle and oocyte development.

Animals↗
PubMed2000

Parity is a major determinant of success rate in medical abortion: a retrospective analysis of 3161 consecutive cases of early medical abortion treated with reduced doses of mifepristone and vaginal gemeprost.

The antiprogesterone mifepristone in combination with a suitable prostaglandin provides an effective method for induction of abortion in early pregnancy up to 63 days of gestation. The combination of 600 mg mifepristone followed by 1 mg of gemeprost vaginal pessary 48 h later is one of the standard regimens in practice, which is registered in several countries in Europe. In 1995, we reduced the doses for both mifepristone and gemeprost to 200 mg and 0.5 mg respectively, as this was shown to decrease significantly the incidence of side effects whilst maintaining a high efficacy. In this article, we report our experience with this regimen in routine clinical practice by analysing 3161 consecutive medical abortions retrospectively. Twelve case notes (0.4%) were not available, and for 310 (9.8%) women, the outcome was not known with certainty as they did not return for their follow up visit. Of the remaining 2839 women, 2732 (96.2%) had a complete abortion following their treatment. One-hundred-two (3.6%) women required an evacuation of the uterus: for incomplete abortion in 63 (2.2%) and ongoing pregnancy in 39 (1.4%). Three women had to undergo surgery for ectopic pregnancies. The surgical intervention rate was significantly higher at gestation of >49 days compared to < or = 49 days (5.7% vs. 2.6%, p = 0.002) and at >56 days than among those at < or = 56 days (6.7% vs. 3.1%; p <0.001). However, for incomplete abortion a significant increase was only seen at gestation >49 days compared to < or = 49 days (3% vs. 1.6%, p = 0.017). The incidence of ongoing pregnancies increased significantly only after 56 days of gestation compared to < or = 56 days (3.8% vs. 0.9%; p <0.001). Parity was related to the outcome with parous women having significantly more incomplete/ongoing abortions compared to nulliparous women (5.4% vs. 2.0%; p <0.001), although parous women did present earlier in pregnancy for termination than nulliparous women (p = 0.01). The incidence of complications was low: 165 (5.8%) women were given antibiotics for presumed genital infection and severe haemorrhage occurred in 11 (0.4%) women, of whom only two required blood transfusion. In summary, the recommended regimen with the reduced doses of mifepristone and gemeprost is highly effective, meeting the anticipated efficacy with a complete abortion rate of >95%. We have concluded from the data that gestation and parity are strong predictors for clinicians to anticipate the probability of a successful medical termination of pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations.

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.

Adolescent↗
PubMed2000

Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men.

Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 microg, 150 microg or 300 microg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 microg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3 x 10(6)/ml), and three men achieving azoospermia in the 300 microg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception.

Administration, Oral↗
PubMed2000

Progesterone withdrawal up-regulates vascular endothelial growth factor receptor type 2 in the superficial zone stroma of the human and macaque endometrium: potential relevance to menstruation.

Several reports indicate that vascular endothelial growth factor (VEGF) expression is increased in endometrial glands and stroma during the menstrual phase in the human endometrium. Here we report that VEGF receptor type 2 (KDR), normally expressed only in the vascular endothelium, was dramatically up-regulated in the stromal cells of the superficial endometrial zones during the premenstrual phase in both human and macaque endometrium. This increase was detectable by Northern analysis, in situ hybridization, and immunocytochemistry and was cell specific, zone specific, cycle phase specific, and VEGF receptor type specific. That is, it only occurred during the premenstrual/menstrual phase, did not occur in glandular epithelium, endothelium, or stromal cells of the deepest endometrial zones, and was not observed for VEGF receptor type 1. The upregulation of stromal KDR was induced by progesterone (P) withdrawal in both women and macaques, and adding back P 24 h after P withdrawal in macaques blocked stromal, but not vascular, endothelial KDR expression. Promatrix metalloproteinase-1 (MMP-1) was coordinately up-regulated in the same stromal cell population by P withdrawal. Because of reports that VEGF can enhance MMP expression, we hypothesize that VEGF-KDR interactions may influence MMP expression in the superficial zones of the primate endometrium during the premenstrual phase, and that these interactions play a role in the induction of menstruation.

Adult↗
PubMed2000

Overview of advances in contraception.

For most of man's existence, natural checks on fertility ensured that the numbers of the population more or less matched the resources available. It is only in the last few generations that man has so dominated the natural environment that the numbers of people in the world have increased exponentially, unchecked by natural disasters such as disease and starvation. Coincidental with extended life expectancy, the fertility rate of individual women has increased with the advent of bottle feeding and the decline in the contraceptive effects of breast feeding. Contraception has become increasingly important to individuals, allowing them to break free from the 'burden of excessive fertility'.

Angiogenesis Inhibitors↗
PubMed2000

Mode of action of medical methods of abortion.

Several pharmacologic agents capable of inducing abortion have become available in the last 20 years. Prostaglandins cause powerful contractions of the uterus that lead eventually to expulsion of the fetal or embryonic tissue, but their effects on smooth muscle elsewhere in the body lead to such troublesome side effects as vomiting and diarrhea. Antimetabolites such as methotrexate inhibit DNA synthesis in rapidly dividing cells such as the trophoblast, resulting in release of prostaglandins and cytokines, extravasation of blood into the decidua, uterine contractions, and expulsion of embryonic or fetal tissue. Drugs that inhibit the synthesis of progesterone (epostane) or block its receptor (mifepristone) reverse the dominant influence of progesterone during pregnancy. As a result, a cascade of events is initiated, including influx of leukocytes and red blood cells into the decidua, release of prostaglandins and cytokines, and uterine contractions. Addition of uterotonic agents such as prostaglandins results in powerful uterine contractions, which supplement those induced by the withdrawal of progesterone. Because these methods reproduce many of the same physiological changes, clinical management of medical abortion is similar to that of spontaneous abortion. These methods provide a useful alternative to surgical abortion in early pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Preliminary experience of the use of a gonadotrophin-releasing hormone antagonist in ovulation induction/in-vitro fertilization prior to cancer treatment.

Therapeutic regimens for the treatment of malignant disease may compromise future fertility. One approach to circumvent this is the cryopreservation of embryos created before treatment for the malignancy. Conventional regimens using gonadotrophin-releasing hormone (GnRH) agonists are time consuming, requiring pituitary down-regulation before gonadotrophin administration, thus the duration of treatment is approximately 20-30 days. GnRH antagonists, however, do not cause an initial stimulation of gonadotrophin secretion and can thus be administered during the later stages of follicular maturation to prevent premature luteinization and ovulation. The duration of ovulation induction/in-vitro fertilization (IVF) treatment is thus reduced. In this study, case histories are reported of six women with newly diagnosed malignancies who requested ovulation induction/IVF prior to chemotherapy or surgery in which we have used the GnRH antagonist Cetrorelix. Gonadotrophin administration was started in the early follicular phase, and Cetrorelix (0.25 mg s.c. daily) was added from day 6 of treatment. Subsequent to human chorionic gonadotrophin (HCG) administration oocytes were recovered and successful fertilization and embryo cryopreservation was achieved in all cases. The median duration of treatment was 12 days (range 8-13, including induction of luteolysis in two patients). These results illustrate the potential use and advantages of a GnRH antagonist in ovulation induction/IVF when the need for immediate initiation of treatment and its duration are critical factors.

Adult↗
PubMed1999

An international study on the acceptability of a once-a-month pill.

Totals of 450 women attending family planning clinics in Hong Kong, Shanghai and Edinburgh, and 468 in Cape Town, completed a questionnaire designed to seek their views on a contraceptive pill which would be taken only once each month. At least two-thirds of the women in all centres liked the idea of a once-a-month pill. In Hong Kong, Cape Town and Edinburgh, women preferred a pill which inhibited ovulation to one which inhibited implantation, while in all centres a pill which worked after implantation (early menstrual inducer) was considered unacceptable by over half the women. A pill which was taken after a missed menstrual period was considered preferable in all centres, perhaps because it would not be used every month but rather only if pregnancy had occurred. No demographic characteristics, contraceptive experiences or beliefs were consistently correlated with attitudes towards a once-a-month pill, except that women who would not consider having an abortion were more likely to dislike a method that either prevented, or worked after, implantation. A once-a-month pill is now technically possible, although the major drawback is the need to determine when it should be taken. It is reassuring that many women from a variety of different cultures and with widely different experiences, would find this an attractive approach to contraception.

Abortifacient Agents↗
PubMed1999

Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C.

We have previously demonstrated that ovarian function and fertility can be preserved in sheep after castration by autotransplantation of cryopreserved strips of ovarian cortex. In the current experiments we have investigated the long term survival of such grafts by detailed measurements of ovarian function for a period of nearly 2 yr after autotransplantation. After ovariectomy and transplantation of frozen/thawed grafts, the concentrations of FSH and LH rose to castrate levels for about 14 weeks before falling gradually to reach near-normal levels at about 60 weeks. In the breeding season from October 1994 to March 1995, all ewes had 5-10 estrous cycles that were similar in length to those in the 4 control ewes. Luteal function as indicated by the progesterone concentration was identical before and 11 months after transplantation. In contrast, the basal concentrations of FSH and LH were persistently raised throughout the luteal phase, but showed a normal decline during the follicular phase. The concentration of inhibin A in ovarian venous plasma measured at the end of the experiment 22 months after transplantation was significantly lower than that in control ewes (mean +/- SE, 409 +/- 118 vs. 1914 +/- 555 pg/ml; P < 0.004). Transplantation of frozen/thawed ovarian tissue to SCID mice demonstrated that about 28% of primordial follicles survived the procedure. All of the ovaries transplanted into sheep contained large antral follicles and/or cysts, but very few primordial oocytes when recovered at autopsy after 22 months. These results demonstrate that despite a drastic reduction in the total number of primordial follicles, cyclical ovarian function is preserved in sheep after autotransplantation of frozen/thawed ovarian tissue and provide experimental confirmation that such a technique could provide a means of preserving fertility in women undergoing chemo- or radiotherapy for malignant disease.

Animals↗
PubMed1999

Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy.

The role of progesterone (P4) in the regulation of inflammatory mediators interleukin-8 (IL-8), monocyte chemoattractant protein-1, and cyclooxygenase-2 (COX-2) and in the recruitment of leukocyte subpopulations in the endometrium has been examined, by employing a model of P4 withdrawal and maintenance in vivo. Messenger RNA and protein expression have been investigated in endometrial biopsies: 1) during the midsecretory phase (LH+8 to 10); during the maintained luteal phase (P4 administered vaginally for 4 days from LH+8) and biopsies collected 2) 24 h and 3) 48 h post withdrawal of P4; and 4) during pseudo pregnancy (lifespan of corpus luteum extended by 7 days with CG; (decidua collected from women with 5) an ectopic gestation and 6) from women undergoing first-trimester termination of pregnancy). CD56+ large granular lymphocytes remain the major leukocyte subtype, both 24 and 48 h after P4 withdrawal, and in decidua (CG supported or ectopic). Higher numbers (P < 0.05) of macrophages (CD68+) were present in endometrium 48 h post P4 withdrawal and in pseudo pregnant endometrium, compared with normal decidua. Significantly more macrophages (P < 0.01) were present in decidua from an ectopic pregnancy. A significant elevation of IL-8 (P < 0.01) and COX-2 (P < 0.05) messenger RNA was detected 48 h post P4 withdrawal. Evidence is provided for up-regulation of IL-8 and COX-2 in response to P4 withdrawal.

Chemokine CCL2↗
PubMed1999

7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men.

The synthetic steroid 7alpha-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5alpha-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted s.c. into the upper arm and removed after 6 weeks and two injections of TE (200 mg, i.m.) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 +/- 0.1 nmol/L after 3 weeks and 1.3 +/- 0.1 nmol/L after 6 weeks (mean +/- SEM; all men). Nadir testosterone concentrations were 3.6 +/- 0.6 nmol/L at the end of the wash-out phase and 9.4 +/- 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential androgen replacement therapy.

Adult↗