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Biomedical subjects

M I Whitehead

Publications and source records attributed to M I Whitehead.

At least 55 records · Page 3Linked to original sources
PubMed1992

Management of the menopause.

The management of the peri- or postmenopausal patient, whether symptomatic or asymptomatic, involves a careful assessment of the problems and expectations of each patient and the matching of appropriate treatment to their needs. The effects of the menopause and its treatment on the patient's immediate and long-term health must be taken into account. This may involve consideration of aspects of medical topics as diverse as gynaecological endocrinology, bone metabolism, oncology and cardiology. Although the benefits of oestrogen therapy are well established the response to therapy must be carefully monitored. Vigilance in the monitoring and seeking out of adverse effects both in individuals and populations must continue to ensure that any problems with this form of therapy are detected at the earliest possible stage.

Climacteric↗
PubMed1991

Detection of endometrial cancer by transvaginal ultrasonography with color flow imaging and blood flow analysis: a preliminary report.

A prospective study was undertaken to assess whether changes in uterine blood flow could be used to detect endometrial cancer in 138 selected postmenopausal women (34 had uterine bleeding, 17 with endometrial cancer; 104 did not have uterine bleeding; 1 had endometrial cancer). Thirty-five of the asymptomatic women were receiving estrogen replacement therapy (ERT). The endpoints were endometrial (including tumoral) thickness and a pulsatility index (PI) derived from flow velocity waveforms recorded from both uterine arteries and from within a tumor. We found an overlap in endometrial thickness between those women with endometrial cancer and those without. The mean arterial PI value was invariably lower in women with postmenopausal bleeding and endometrial cancer (mean 0.91, range 0.31-1.49) than in those with other reasons for the blood loss (mean 3.83, range 1.95-6.40). The index was 1.10 in the woman with endometrial cancer but no sign of postmenopausal bleeding. Blood flow impedance was inversely related to stage of cancer. PI values in healthy women tended to increase slightly with age, but decrease during ERT. The detection rate was 100% within the limitations of the study design, and the false-positive rate was 1% for all women not receiving ERT and 11% for patients receiving ERT. Malignant tumors show signs of altered vascularization and a low PI (mean 0.49, range 0.29-0.92). We conclude that transvaginal ultrasonography, with or without color flow imaging, and blood flow analysis can be used to detect endometrial cancer in women with postmenopausal bleeding. A screening procedure for asymptomatic women must allow for changes in uterine blood flow during ERT.

Aged↗
PubMed1991

Ultrasound screening for familial ovarian cancer.

We have used transvaginal ultrasonography to screen 776 asymptomatic women for familial ovarian cancer. Every woman had at least one first- or second-degree relative develop the disease (677, 87%; and 98, 13%, respectively). The mean age of the study population was 51 years (range, 24 to 78 years); 52% were premenopausal, 36% were naturally postmenopausal, and 12% had undergone a hysterectomy. Overall, 43 women (5.5%) were referred for surgical investigation and 39 had a laparatomy. Nineteen/thirty-nine (48%) had bilateral ovarian masses, and 15% of abnormal ovaries had more than one type of histopathology. Twenty-three tumors and thirty-two tumor-like conditions were detected. There were 3 cases of primary ovarian cancer (prevalence, 3.9/1000), all FIGO stage Ia. None of the women has developed ovarian cancer within the first year of the scan (giving a provisional detection rate of 100%). The false positive rate was 40/773 (5.2%), the predictive value of a positive screen result was 7.7%, and the odds in favor of finding any mass at laparotomy were about 19 to 1 or for any tumor, 1 to 1. At surgery the odds against finding primary ovarian cancer were 12 to 1. The positive predictive value of the screening procedure and the prevalence of the disease were significantly higher than the corresponding values from a previous population-based screening program.

Adult↗
PubMed1991

The long-term risks and benefits of hormone replacement therapy.

There is increasing awareness that the long-term consequences of ovarian failure can be prevented or reduced with appropriate hormone replacement therapy (HRT). After the menopause, there is a rapid loss of trabecular bone resulting in a one in two lifetime risk of osteoporotic fracture. HRT prevents this bone loss and decreases the incidence of fracture. A minimum of 5 years treatment is recommended for significant benefit. Epidemiological evidence is accumulating that post-menopausal oestrogen therapy reduces the risk of cardiovascular disease and stroke by between 30 and 70% even in the presence of established risk factors. Given the prevalence of cardiovascular disease, this is likely to be one of the principle benefits of HRT in the next decade. Concerns about the long-term safety of HRT have focused on endometrial and breast cancer. The increase in risk of endometrial cancer associated with oestrogen only therapy is abolished with the sequential addition of a progestogen for 10-12 days each cycle. The possible effect of HRT on breast cancer risk has to be considered against the background of a one in 12 lifetime risk of developing this disease. The epidemiological studies investigating this relationship are reviewed in this paper. There is a broad consensus that 5-6 years duration of HRT does not increase breast cancer risk. Longer durations of therapy (10-15 years) have been reported to increase this risk although not all the data are in agreement. Other factors, such as family history and benign breast disease, may also influence the risk of breast cancer. The potential benefits of HRT on mortality and morbidity are enormous. Against this is a possible small increase in breast cancer risk with long-term usage. Greater awareness of the long term consequences of the menopause and the potential benefits of HRT should be encouraged so that women can make informed decisions about their need for HRT.

Breast Neoplasms↗
PubMed1991

Genetic epidemiology of ovarian cancer: segregation analysis.

The genetic epidemiology of ovarian cancer has been investigated by complex segregation analysis of 462 pedigrees ascertained through a normal consultant. The observed pattern of ovarian cancer is compatible with an autosomal dominant gene. The gene frequency of the abnormal allele is 0.0015-0.0026 with a lifetime penetrance of 0.74-0.79. The gene frequency accounts for a significant proportion of ovarian cancer in young women. By age 70 the majority of affected women are phenocopies. The results from this analysis should enable the risks of ovarian cancer to be more accurately estimated than by empiric methods for relatives of affected women, and can maximize the usefulness of screening programmes and future linkage studies.

Adult↗
PubMed1990

Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women.

66 early postmenopausal women were randomised to 28-day cycles of either transdermal hormone replacement therapy--continuous oestradiol 17-beta 0.05 mg daily, with norethisterone acetate 0.25 mg daily for 14 of each 28 days--or oral therapy--continuous conjugated equine oestrogens 0.625 mg daily, with dl-norgestrel 0.15 mg daily for 12 of each 28 days. An untreated reference group of 30 women were studied concurrently. Bone density was measured in the lumbar spine and proximal femur by dual photon absorptiometry at 6-month intervals for 18 months. Skeletal turnover was assessed by serum measurements of calcium, phosphate, and alkaline phosphatase, and by urine estimations of hydroxyproline/creatinine and calcium/creatinine excretion. In both treatment groups by comparison with the untreated groups by comparison with the untreated group, bone density increased in the vertebrae and proximal femur and biochemical measurements indicated a significant reduction in bone turnover.

Absorptiometry, Photon↗
PubMed1990

Prolonged endometrial stimulation associated with oestradiol implants.

OBJECTIVE: To provide information on endometrial stimulation after discontinuation of treatment with oestradiol implants. DESIGN: Long term follow up of withdrawal bleeding patterns in women taking progestogens cyclically every month after oestradiol implant treatment was ended. SETTING: Specialist menopause clinic. SUBJECTS: 10 Postmenopausal patients (at least 12 months' amenorrhoea after the last spontaneous period) who were treated with oestradiol implants for typical symptoms of oestrogen deficiency. The oestradiol dose was 50 mg, reimplantation occurring roughly every six months. Patients subsequently either needed to discontinue the hormone treatment for medical reasons or expressed a desire to stop treatment. MAIN OUTCOME MEASURE: Duration of endometrial stimulation--defined as the presence of withdrawal bleeding in response to progestogen given cyclically--after insertion of the last oestradiol implant. RESULTS: Four patients eventually stopped bleeding, their mean duration of bleeding being 35 months (range 27-43 months). One patient required hysterectomy 26 months after the last implantation because of persistent irregular bleeding despite treatment with high doses of progestogen. Three patients bled for 22, 30, and 36 months and then restarted oestrogen treatment because symptoms returned. The last two patients subsequently continued to bleed 12 and 21 months after the last implantation. CONCLUSIONS: The duration of endometrial stimulation after implantation can be prolonged, up to 43 months. Insertion of oestradiol implants can carry a long term commitment to the cyclical administration of progestogen and regular withdrawal bleeding if endometrial hyperplasia and carcinoma are to be avoided.

Adult↗
PubMed1990

Transdermal administration of oestrogen/progestagen hormone replacement therapy.

The effects of an oestrogen/progestagen transdermal therapeutic system (TTS) were evaluated in sixteen oestrogen-deficient women. The patients applied conventional oestradiol-TTS for 14 days, then two combined norethisterone acetate/oestradiol patches for a further 14 days. The treatment was repeated for five cycles. Ten patients then underwent metabolic studies. One patient had amenorrhoea, but the rest experienced regular withdrawal bleeding which was seldom heavy. Fourteen endometrial biopsy samples were taken during the fifth treatment cycle; none showed proliferative or hyperplastic features. The effects of transdermal norethisterone acetate on symptoms, lipid metabolism, and psychological status were determined by comparing features in the oestrogen-only phase and in the combined phase; the effects were very mild. These preliminary findings show that transdermal progestagen can be successfully administered in hormone replacement therapy to prevent endometrial proliferation while minimising the adverse effects that may be seen with oral administration.

Administration, Cutaneous↗
PubMed1990

The optimal dose of oral norethindrone acetate for addition to transdermal estradiol: a multicenter study.

The effects of adding one of three doses (0.5, 0.75, or 1.0 mg/d) of norethindrone acetate for 12 days each month to continuous, transdermal estradiol (0.05 mg/d) have been determined in a prospective, randomized, multicenter study. Significant symptomatic and psychological improvements were observed and, with one exception, were not opposed by the added progestogen. Distinct redness at the site of last patch application was reported by 10% of patients and faint erythema by 30%. However, less than 5% of patients discontinued treatment because of skin problems. Breakthrough bleeding occurred infrequently and all three doses of norethindrone acetate induced a regular pattern of bleeding with secretory transformation in the endometrium. There was no hyperplasia or carcinoma.

Administration, Cutaneous↗
PubMed1990

Novel screening strategies for early ovarian cancer by transabdominal ultrasonography.

Data collected during a prospective study to assess the efficacy of detecting early ovarian cancer by transabdominal ultrasonography have been used to refine and extend the screening procedure. The analysis was based on results from 5479 self-referred asymptomatic women, who were scheduled to undergo three annual screens consisting of one or more ultrasound scans. A positive result (based mainly on the presence of abnormal morphology) was obtained at 338 screens (326 women). Five patients with primary ovarian cancer (four stage 1a, one stage 1b; two at screen 1, three at screen 2) were identified (prevalence 0.09%). The apparent detection rate was 100% and the false-positive rate (FPR) was 3.5% at screen 1 and 2.3% overall. The use of abnormal morphology, or the maximum ovarian volume (MOV) greater than 96th centile as alternative criteria for a positive screen result, together with a defined volume change at rescan (VC) would give a FPR of 3.1% at screen 1 and 2.0% overall. The use of abnormal morphology alone at scan 1 and VC at rescan would give an overall FPR of 1.6%. The odds that a positive screen result would indicate the presence of an ovarian mass, a benign tumour, any ovarian cancer or primary ovarian cancer would be about 4 to 1, 2 to 1, 1 to 26, and 1 to 50 respectively. The results provide a more rational basis for the application and development of screening procedures for early ovarian cancer in both pre- and post-menopausal women.

Adolescent↗
PubMed1990

Effect on plasma lipids and lipoproteins of postmenopausal oestrogen therapy with added dydrogesterone.

In a prospective, randomized, cross-over study, 14 postmenopausal women completed 9 months of treatment with conjugated equine oestrogens, 1.25 mg daily. Seven women added dydrogesterone 20 mg daily for 12 days during months 2, 3 and 4, and then 10 mg daily for an identical time in months 5, 6 and 7. The other seven women added the two dydrogesterone doses in reverse sequence. No dydrogesterone was taken during months 8 and 9. Lipids and lipoproteins were measured before treatment and at the end of months 4, 7 and 9. Lipids were also estimated in an untreated (reference) group of eight postmenopausal women on two occasions 6 months apart; these showed significant changes in HDL2- and HDL3-cholesterol. In the treatment group, HDL-cholesterol and apolipoprotein (apo) A1 were significantly higher and LDL-cholesterol and apo B were significantly lower at months 4, 7 and 9 compared with baseline values. Triglyceride levels were increased significantly over baseline values, but remained within the normal range. No significant differences between the two dydrogesterone doses were observed on any lipid and lipoprotein fraction, nor were there any differences between the oestrogen-only and oestrogen/dydrogesterone treatment phases. Dydrogesterone appears to cause little, if any, lipid and lipoprotein changes and assessment in a larger population of postmenopausal women is warranted.

Dydrogesterone↗
PubMed1990

Endometrial, physical and psychological effects of postmenopausal oestrogen therapy with added dydrogesterone.

Sixteen postmenopausal women receiving conjugated equine oestrogens 1.25 mg/day, continuously, were randomly allocated to add dydrogesterone 20 mg/day for 12 days each calendar month for 3 months and then 10 mg/day in an identical fashion for a further 3 months, or to receive the dydrogesterone doses in reverse sequence. The effects of the two dydrogesterone doses on endometrial histology, vaginal bleeding, and the symptomatic and psychological status were compared. Endometrial samples were obtained around day 10 of progestogen addition. Dydrogesterone, 20 mg, induced uniform, late secretory transformation in all samples; with 10 mg one sample showed mixed early and late secretory features and another demonstrated late secretory changes associated with atypical hyperplasia. Both dydrogesterone doses induced an acceptable withdrawal bleed; most bleeding episodes were 'spotting' or normal in amount, and heavy bleeding was reported infrequently. There was one episode of breakthrough bleeding. There were no differences in bleeding patterns between the two dose regimens. Anxiety, and the physical and psychological status were significantly improved after 3 months of therapy. Significant benefits on depression were observed less clearly. There were no differences between the two dydrogesterone doses on anxiety, depression and the physical and psychological status, and, overall, the addition of the progestogen did not antagonize oestrogen benefits.

Affective Symptoms↗
PubMed1990

The role and use of progestogens.

Certain epidemiologic, histologic, and biochemical data on the effects of estrogens and progestogens on the endometrial, physical, psychological, and lipid status of postmenopausal women are reviewed. Unopposed estrogen replacement increases the risk of endometrial cancer not only while treatment is being taken but also for many years after it is discontinued. Strategies must be developed for posttreatment surveillance. The addition of a cyclic progestogen reduces this risk, but it is not clear whether the reduction is to, or below, that observed in an untreated population. Protective doses of C-19 (norethindrone) and C-21 (medroxy-progesterone acetate) progestogens are suggested. All progestogens may cause physical, psychological, and metabolic side effects. In addition, most women taking cyclic progestogens experience regular withdrawal bleeding. Continuous/combined therapy has been introduced to minimize these side effects and induce amenorrhea. Published data on the efficacy and safety of continuous combined therapy are few. Although the regimen is effective in relieving menopausal symptoms and inducing endometrial atrophy in most patients, side effects of progestogen are common and there is a high incidence of bleeding in the first few months, which is unacceptable to many patients. In our view, the effect of continuous combined therapy on lipids and lipoproteins has not been properly addressed. Based upon the available literature, we believe that the enthusiasm for continuous combined therapy is premature and we urge caution in its use until further, more conclusive, data become available.

Drug Administration Schedule↗