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Biomedical subjects

J W Studd

Publications and source records attributed to J W Studd.

At least 19 recordsLinked to original sources

Five-year changes in bone density, and their relationship to plasma estradiol and pretreatment bone density, in an older population of postmenopausal women using long-term estradiol implants.

The aim of this study was to observe whether bone mineral density (BMD) improves over 5 years in older women using estradiol implants. A total of 18 women were selected who had commenced hormone replacement therapy (HRT) around the age of 60 years. The median age was 60.9 years (range 59.7-63.2 years). Each woman had a pretreatment bone scan and then received 6-monthly subcutaneous 50 mg estradiol implants. Twelve untreated women were also selected who had had bone scans at baseline and after 5 years. A comparison of the changes in BMD between treated and untreated women was made using the Wilcoxon rank-sum test. All changes at the hip and spine were statistically significant improvements from baseline in the estradiol-treated group. After 5 years of treatment, the estradiol-treated group had significantly improved bone mineral densities compared with the untreated group. At the spine, the plasma estradiol concentration is statistically significantly correlated with the 5-year increase in bone density (r = 0.717, p = 0.004). There was found to be an inverse relationship between the percentage increase in BMD over the 5-year period and initial bone density (r = -0.635, p < 0.005). Thus estrogen is seen to have the effect of improving bone density in older women over 5 years of treatment. The increase in vertebral bone density is most marked in those women with the highest plasma estradiol levels and the lowest pretreatment bone density.

Bone Density↗

Reduced bone mineral density in HIV-positive individuals.

A total of 105 HIV-positive patients underwent dual-energy X-ray absorbtiometry (DEXA) scan to assess bone mineral density (BMD). The prevalence of reduced BMD was found to be 71% and was higher in patients who had ever been treated with protease inhibitors (PI). Our results suggest a possible association between PI and reduced BMD, and further complicate the debate regarding when to commence treatment of HIV and with what agents to start.

Absorptiometry, Photon↗

Urogenital prolapse and atrophy at menopause: a prevalence study.

For 285 subjects referred to a menopause clinic data were prospectively collected on the time elapsed since the onset of menopause (menopausal age), sexual activity, dyspareunia, smoking, chronic cough and constipation. Prolapse and atrophy were sought on examination. FSH assay confirmed menopausal status. We found an anterior wall prolapse in 51% of the subjects, of which 6% were protruding beyond the introitus. Posterior wall prolapse was present in 27% and apical prolapse in 20%; none was protruding beyond the introitus. No trend was noted between prolapse and menopausal age. Atrophy was evident in 34% of the women, and this was related to menopausal age (P<0.001). Forty per cent of the sexually active women admitted to dyspareunia, of which 2/3 were superficial. This correlated with advancing menopausal age (P<0.02). In conclusion, genital prolapse was frequent in the population of postmenopausal women, predominantly cystocele, but the prevalence did not correlate with menopausal age.

Adult↗

Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic.

OBJECTIVE: To assess the usage of both conventional and complementary therapies by peri- and postmenopausal women for the treatment of menopausal symptoms. METHOD: A prospective questionnaire was completed by 200 consecutive patients attending a tertiary referral London-based specialist menopause clinic between September and December 1999. RESULTS: The median age of responders was 53.5 years (interquartile range 49-59). In total 137 women (68.5%) had ever tried an alternative treatment for the relief of their menopausal symptoms. Of these women 66% were regular users and 62% were satisfied with the effects of treatment. Women younger than the median age were significantly more likely to have used complementary therapies than older women (p = 0.036). Of the 200 participants, 184 women (92%) were current users of conventional hormone replacement therapy (HRT), and 89% were satisfied with the effects that their current HRT regimen had on their menopausal symptoms. Age was not related to satisfaction with conventional or complementary medicines. General practitioners and hospital doctors accounted only for 17% and 9%, respectively, of the primary sources of information for complementary medicines. CONCLUSIONS: High rates of usage and satisfaction were found with both conventional and complementary treatments for the relief of menopausal symptoms in our unit. For many of the women, both types of medicine are taken concurrently. Both general practitioners and hospital doctors are poor primary sources of information on complementary therapies for menopausal women.

Ambulatory Care Facilities↗

Plasma leptin concentrations are increased in women with premenstrual syndrome.

Leptin is a metabolic regulator of the hypothalamic- pituitary-gonadal axis, and plays an important role in human reproduction. Its neuro-endocrine effects are mediated by interactions with receptors in the hypothalamus, where emotional drive is also controlled. We postulated that circulating leptin concentrations are increased in premenstrual syndrome (PMS), and that this may be associated with the psychological symptoms of the disease. We obtained fasting venous samples from 32 women with PMS and 28 women with asymptomatic menstrual cycles, matched for age, body mass index and menstrual cycle length. Leptin concentrations were measured by radioimmunoassay. Leptin concentrations increased significantly during the luteal phases of the menstrual cycles of the control and PMS groups as compared with the follicular phase, having excluded the 11 women with PMS and six controls found to be anovulatory on the basis of mid-luteal plasma progesterone concentrations from the analysis. A greater increase was observed in women with PMS than the controls (P: = 0.00006 and 0.003 respectively). Although leptin concentrations in the follicular and luteal phases were higher in PMS than the controls, the difference was only statistically significant between the follicular phases (P: = 0.001). There was no clear relationship between leptin and oestradiol or progesterone in this study. These findings suggest that leptin may play a role in the pathophysiology of the disease, and requires further evaluation.

Adult↗

The feto-placental unit stimulates the pregnancy-associated increase in maternal bone metabolism.

The aim of the study was to investigate role of the feto-placental unit in the pregnancy-induced increase in maternal bone metabolism. To achieve this, circulating concentrations of carboxy terminal pro-peptide of type I pro-collagen (PICP, a marker of bone formation) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP, a marker of bone resorption) were measured in three groups of pregnant women. Group 1 comprised 12 women with singleton pregnancies; group 2, nine women with twin pregnancies; and group 3, 19 women with multifetal pregnancies (> or =3 fetuses) before and after selective fetal reduction to twin pregnancies. Blood samples were obtained at 10-12 weeks gestation (groups 1-3, pre-fetal reduction in group 3) and 4 weeks and 8 weeks later (groups 2 and 3). Before fetal reduction there was a significant correlation between the number of fetuses and the concentrations of both PICP and ICTP (r = 0.503 and P = 0.001 and r = 0.573 and P < 0.001 respectively). The circulating concentrations of PICP and ICTP were significantly higher in the pre-reduction multifetal pregnancies than in the twin pregnancies (P < 0.001 and P = 0.0013 respectively). The circulating concentrations of ICTP in multifetal pregnancies fell by 4 weeks after fetal reduction to those observed in control twins. Concentrations of PICP were unaltered after fetal reduction. Higher order multiple pregnancies had the greatest decline in ICTP concentrations. These data suggest that the increased bone turnover observed in the multifetal pregnancies is due to a factor derived from the feto-placental unit and that this factor acts primarily to stimulate bone resorption.

Biomarkers↗

Fibroid embolisation: a technique not without significant complications.

Uterine artery embolisation is a new minimally invasive technique used for the treatment of fibroids. Twenty-one women underwent bilateral uterine artery embolisation at our unit, and we assessed the efficacy, morbidity and patient satisfaction with the procedure. Mixed outcomes were found. Reduction in fibroid volume measured by magnetic resonance imaging was impressive, and the majority of women felt their symptoms had improved. One woman achieved a full term pregnancy following the procedure. However, the procedure involved a significant inpatient stay, analgesia requirement, and a slower recovery time than anticipated. One woman died following overwhelming sepsis occurring 10 days after the procedure. Further studies are required to assess the role this technique may play in the management of uterine fibroids.

Adult↗

A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women.

OBJECTIVE: To determine the pharmacokinetics of a progesterone cream following short and long term dermal administration. DESIGN: Single-centre, randomised, multiple-dose, open-label study. SETTING: Reproductive Medicine Trust, London. POPULATION: Twenty-four healthy postmenopausal women aged between 40 and 65 years were recruited through an advertisement in a local newspaper. METHODS: The women were randomly allocated to progesterone cream 40 mg daily or 20 mg, twice daily, for 42 days. MAIN OUTCOME MEASURES: The concentration of progesterone in the serum was measured on days 1 and 42 before the morning dose, and at 2, 4, 6, 12 and 24 hours after the morning dose. Serum follicle stimulating hormone, oestradiol, testosterone and urinary pregnanediol-3-glucuronide were also measured on days 1 and 42. RESULTS: Three subjects dropped out before using the cream and two more dropped out after the first treatment leaving a reportable sample of 19 women. There was a rise in the mean progesterone concentration at each sampling time between days 1 and 42. There was evidence of a rise in pregnanediol-3-glucuronide over the course of the study. There was no change in follicle stimulating hormone, oestradiol or testosterone. There was no difference between the two regimens. CONCLUSIONS: Transdermal progesterone (40 mg) per day for 42 days causes a small increase in serum progesterone concentration, although there is wide variation. Whether such levels are of clinical benefit remains to be seen.

Administration, Topical↗

The psychological outcome of hysterectomy.

The objective of this study is to review the published literature on psychological outcome of hysterectomy and oophorectomy for non-malignant indications. The relevant publications over the past 30 years until the end of 1997 were identified by a MEDLINE computer search. This was followed by hand searches of the relevant references in the literature identified by the electronic search. The published studies on the psychological outcome of hysterectomy have been selected to identify the incidence, possible causes and risk factors of psychological morbidity, and the measures that can be adopted to improve the outcome. The study showed that the majority of retrospective studies reported an adverse psychological outcome after hysterectomy. However, all prospective studies showed that the incidence of depressed mood is higher even before hysterectomy, owing to pre-existing psychiatric illness and personality and psychosocial problems, as a result of the emotional response to gynecological symptoms or as a manifestation of associated ovarian failure. Hence, the therapeutic effects of hysterectomy include improvement of mood in some but not all patients, unless proper case selection, psychiatric evaluation and preoperative counselling are arranged. An early detection of ovarian failure after hysterectomy, the initiation of hormone replacement therapy (HRT) immediately after surgery in perimenopausal women and in those undergoing oophorectomy, as well as regular follow-ups to ensure long-term compliance with HRT, would also improve the psychological outcome. In conclusion hysterectomy itself is not the cause of any adverse psychological outcome. Psychological symptoms actually improve in the majority of women, with the relief of distressing gynecological symptoms and the correction of ovarian hormone deficiency, but hysterectomy may not be of any benefit in women with prior psychiatric illness and those with personality and psychosocial problems.

Affect↗

Comparison of the biochemical effects of testosterone and estrogen on bone markers in surgically menopausal women.

Twenty-five women with a previous total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH BSO) were given estradiol 50 mg implants at baseline, followed at 16 weeks with the combination of estradiol 50 mg and testosterone 100 mg. Blood samples were taken at 8-weekly intervals over 32 weeks. Serum levels of estradiol, testosterone, sex hormone binding globulin (SHBG) and agents involved in skeletal growth (growth hormone (GH), insulin-like growth factor 1 (IGF-1), carboxy terminal pro-peptide of type 1 pro-collagen (PICP; a bone formation marker) and cross-linked carboxy terminal telopeptide (ICTP; a marker of bone resorption)) were measured. Serum PICP levels increased significantly after estradiol alone (p = 0.0032) but the addition of testosterone had no significant effects on bone markers GH and IGF-1. These biochemical changes confirm previous studies, which found that the addition of testosterone did not augment the effect of estradiol implants on bone mineral density. Although physiological hormone replacement therapy in oophorectomized women would include replacement of both estradiol and testosterone, this may not to be necessary for prevention of osteoporosis where adequate serum estradiol levels are reached.

Adult↗

The long-term tolerability and efficacy of OESCLIM: results of a 1-year study.

OBJECTIVES: A 1-year, open-label, non-comparative study evaluated the long-term tolerability and acceptability of a new generation matrix patch in post menopausal women with estrogen deficiency. METHODS: Menopausal women (224) from 37 centres in five European countries received OESCLIM 50 microg/d (17-beta estradiol) for 3 months, titrated if necessary to either 25 or 100 microg/d for a further 9 months. Patients received either a continuous or discontinuous estradiol regimen with concomitant sequential progestogen (except hysterectomised patients). Skin tolerability was assessed by patient diaries and questionnaires. Global tolerability, efficacy, laboratory parameters and global acceptability were also monitored. RESULTS: Almost two-thirds of women did not experience any kind of skin reaction and only 4.3% of all applications (752/17,702) caused site reactions. Of these, the majority caused only slight or no discomfort (63.2%). Only 0.37% of total applications required patch removal; none required therapy. A low percentage of patients withdrew due to tolerability issues: 2.7% due to skin reactions; 7.5% due to hyperestrogenism. The mean number of hot flushes experienced by symptomatic women reduced by 91% from 4.0 at baseline to 0.4 after 2 months. Total cholesterol reduced by 3.9% and LDL cholesterol by 5.1%, with no increase in triglyceride levels. Investigators assessed treatment as effective in 96.8% of cases; well tolerated locally in 93.1% and well tolerated generally in 89.5%. At the end of this 1 year study, 79% of patients wished to continue therapy. CONCLUSION: OESCLIM is well tolerated locally and systemically in long-term therapy with a high proportion of patients wishing to continue therapy after 1 year.

Administration, Cutaneous↗

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Administration, Oral↗

Postpartum bone mineral density following antenatal dexamethasone therapy.

The aim of this study was to determine whether the changes in bone metabolism, which we have demonstrated previously with antenatal dexamethasone therapy, are associated with a lower bone mineral density. We assessed bone mineral density in the proximal femur and lumbar spine using dual photon X-ray absorptiometry after delivery in 15 women who received dexamethasone therapy for fetal lung maturation, and in 30 women who did not have dexamethasone therapy in pregnancy. The absolute bone mineral density, T scores and Z scores at the proximal femur and lumbar spine were similar, and the median values of T and Z scores were positive in both groups. We conclude that antenatal dexamethasone therapy has no long term effect on bone mineral density.

Absorptiometry, Photon↗

A general practice pilot audit study to assess advice and treatment offered to women following hysterectomy.

BACKGROUND: Current evidence suggests that information and treatment offered to women post-hysterectomy to prevent osteoporosis are poor. OBJECTIVES: To pilot a general practice audit protocol, to assess its ability to identify hysterectomized women and to offer appropriate information on fracture prevention. METHOD: A pilot audit study was designed to assess advice offered to hysterectomized women aged 25-64 years. Data on ovarian status were evaluated. Women were recalled for counselling if there was no evidence of advice on fracture prevention and if they were not taking hormone replacement therapy (HRT). Change in HRT usage was used as the outcome measure to assess the impact of the audit. RESULTS: Baseline data were collated for 5743 women. In 1456 (25%), both ovaries were removed and 4029 (70%) had one or both ovaries conserved; 258 (5%) had incomplete ovarian data. The average age at hysterectomy with both ovaries removed was 43.9 years, and with conservation of one or both ovaries was 40.5 years and 40.1 years, respectively. Some 2888 (50%) were ever-users of HRT (both ovaries removed 70%, one ovary removed 53%, both ovaries conserved 44%). A total of 2083 (36%) were known current users (both ovaries removed 53%, one ovary removed 40%, both ovaries conserved 30%). The mean duration of use in 2620 ever-users was 44 months. This was similar for all the women irrespective of ovarian status. Eighty per cent of those given HRT reported receiving some advice. Seventy-seven per cent of those not given HRT had not received advice. By the end of the audit, 424 had commenced HRT (20% increase). Current use rose to 44% (both ovaries removed 59%, one ovary conserved 46%, both ovaries conserved 39%). Sixty-three per cent of new users chose transdermal preparations. CONCLUSIONS: The mean age at hysterectomy of between 40.1 and 43.9 years indicates the potential for early ovarian failure. Use of HRT is associated with availability of counselling. Uptake was better than anticipated, but HRT usage was still well below optimum. This audit fulfills its objectives but not without cost implications. Year by year it should achieve significantly improved management and health of hysterectomized women, and improved standards of patient care.

Adult↗

Obstetric outcome in 232 ovum donation pregnancies.

OBJECTIVE: To study the obstetric outcome of ovum donation pregnancies. DESIGN: A retrospective analysis of 232 ovum donation pregnancies in the six years from 1988 to 1993. SETTING: Infertility clinic in a private hospital. PARTICIPANTS: All ovum donation recipients that achieved pregnancy in the clinic during the stated time period. MAIN OUTCOME MEASURES: Percentages of live birth and miscarriages and ectopic pregnancies; number of sacs identified in the uterus at early (four weeks after transfer) and later scans; incidence of antepartum and postpartum haemorrhage; incidence of pregnancy-induced hypertension; incidence of preterm, low birthweight and small-for-gestational age babies; and incidence of operative deliveries. RESULTS: Of 232 pregnancies, 151 babies were born (live birth rate of 20%); and 81 were lost (57 before eight weeks, 17 after eight weeks and seven ectopic pregnancies). In nine cases there were no intrauterine sacs at the early scan (two 'chemical pregnancies' and seven ectopic pregnancies). In 169 cases there was initially one intrauterine sac, ending with 102 singleton deliveries (60%); in 47 cases there were initially two intrauterine sacs, ending with 11 singleton deliveries (23%) and 32 twin deliveries (68%); in the seven cases where three sacs were identified initially, there were no singleton deliveries, three twin deliveries (one selective fetal reduction) and three triplet deliveries. Women with premature ovarian failures had a significantly higher pregnancy rate compared with those with functioning ovaries (P < 0.02). However, in the former group, the miscarriage rate was also significantly higher (P < 0.03) so that the number of term births was similar. The incidence of vaginal bleeding was 12% in the first trimester, 1.5% in the second trimester, and 2% in the third trimester. The incidence of postpartum haemorrhage was 12%. Thirty-two women had pregnancy-induced hypertension (23% of all deliveries). This occurred in 22/105 singletons (21%), 7/32 twins (22%) and in all three (100%) of the triplets. In the singleton group 13% of infants were preterm, 18% had a birthweight < 2.5 kg and 15% were < 3rd centile for birthweight at delivery (small-for-gestational age). Ovarian function was found to be the only factor that significantly influenced the incidence of small-for-gestational age babies (odds ratio 8.84; 95% confidence interval 1.1-70.0; P = 0.007). The overall operative delivery rate was 85% with the caesarean section rate being 69%. CONCLUSIONS: Women who become pregnant following oocyte donation should be considered obstetrically as high risk, especially those with ovarian failure because of the increased incidence of small-for-gestational age infants in these pregnancies. They are also at higher risk of pregnancy-induced hypertension and postpartum haemorrhage.

Abortion, Spontaneous↗

Antenatal corticosteroid therapy and risk of osteoporosis.

OBJECTIVE: To assess the risk of maternal osteoporosis associated with antenatal corticosteroid administration for neonatal respiratory distress syndrome prophylaxis. DESIGN: Prospective longitudinal study. SETTING: Maternity unit of Chelsea and Westminster Hospital, London. POPULATION: Fourteen pregnant women who received dexamethasone therapy for fetal lung maturation in anticipation of delivery before 34 completed weeks of gestation. METHODS: Blood samples were collected before dexamethasone administration, 24 hours and 48 hours after the course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the rate of bone formation, and serum levels of cross-linked carboxy terminal telopeptide (ICTP) were measured as a marker of bone resorption. MAIN OUTCOME MEASURES: Changes in the markers of bone turnover following dexamethasone administration. RESULTS: Serum PICP levels dropped 24 hours after dexamethasone therapy (P = 0.001), but partially recovered by 48 hours (P = 0.014) to reach higher than pre-therapy levels at delivery (P = 0.044). Although there were no corresponding changes in the serum levels of ICTP after 24 and 48 hours of therapy, levels increased from pretherapy to delivery (P = 0.006). CONCLUSION: Antenatal corticosteroid therapy leads to a transient suppression of, followed by an increase in, bone formation without any significant alteration in the pattern of bone resorption expected during pregnancy.

Biomarkers↗

The psychotherapeutic effects of estrogens.

The effect of estrogens on the central nervous system, particularly mood and behavior, remains a controversial area which needs clarification, not just for understanding of depression in women but to ensure that such commonplace problems in women have efficient and appropriate therapy. There is now good evidence that estrogens are rapidly effective in the treatment of depression in many women but this information has not found its way through to those health care personnel, psychiatrists and psychologists who are principally involved in the treatment of depression. There is also strong evidence for the benefits of estrogens on cognitive functioning, not only in preventing the onset of dementia but also in improving the symptoms in the established condition. Recent work has also suggested a benefit for estrogens on mood in women diagnosed as suffering from chronic fatigue syndrome. This article reviews the effect of endogenous estrogen on the female central nervous system and the ever increasing evidence for the diverse psychotherapeutic effects of exogenous estrogens.

Antidepressive Agents↗