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Biomedical subjects

M I Whitehead

Publications and source records attributed to M I Whitehead.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins.

OBJECTIVE: We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN: Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS: In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION: Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.

Administration, Cutaneous↗
PubMed1992

Use of family history in a screening clinic for familial ovarian cancer.

We have estimated the risks of ovarian and other types of cancer in first-degree relatives of women who have developed the disease (the index patients). The number of deaths from each type of cancer was determined from pedigrees taken from 391 self-referred, asymptomatic women attending a screening clinic for familial ovarian cancer. These values were compared with the expected number of deaths for women in the general population (calculated from life tables), and the relative risks were used to estimate lifetime risks. The overall relative risk were 4.5, 1.4, 1.3, and 1.1 for ovarian, stomach, breast, and endometrial cancers, respectively. The risks were invariably higher if the index patient was < 55 years old. Ovarian cancer appeared to have no clear inheritance pattern in 290 pedigrees and there was no increased risk for the first-degree relatives. Eighty-two pedigrees were compatible with a diagnosis of a multiple-site cancer family syndrome and the relative risks were 6.1, 2.8, 3.7, and 2.7 for ovarian, breast, stomach, and colorectal cancer, respectively. There was evidence of site-specific ovarian cancer in 19 families; the relative risk for the first-degree relatives was 39.1 and the lifetime risk 1 in 2. We believe that family history can be used to identify women who are at a high risk of developing ovarian and certain other types of cancer. This information can be used to counsel women attending ovarian cancer screening clinics and to maximize the usefulness of current resources.

Female↗
PubMed1992

Correlation in ages at death from familial ovarian cancer among sisters.

The analysis of pedigrees taken from 97 of 1466 women attending a screening clinic for early familial ovarian cancer showed that there was a strong correlation in the ages at death from the disease among sisters (r = 0.68, confidence limits 0.51-0.82, P < 0.001), but not between mothers and daughters. This information can be used to help counsel women who are considering the appropriate time for more intensive screening or prophylactic oophorectomy.

Adult↗
PubMed1992

Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis.

OBJECTIVES: This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. STUDY DESIGN: Seventy-nine postmenopausal women on sequential estrogen-progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. RESULTS: Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. CONCLUSIONS: Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised.

Amenorrhea↗
PubMed1992

Differential effects of transdermal estradiol and sequential progestogens on impedance to flow within the uterine arteries of postmenopausal women.

OBJECTIVE: To investigate the relationship between estradiol (E2), progestogen, and impedance to blood flow in the uterine artery. SUBJECTS: Twelve postmenopausal women treated for two cycles with transdermal E2, 0.05 mg/d, with either norethindrone acetate, 0.7 mg, or medroxyprogesterone acetate, 10 mg added sequentially. MEASUREMENTS: Transvaginal ultrasonography and color flow imaging were used to measure the pulsatility index in the uterine arteries before and during the E2-only and combined E2/progestogen phases. RESULTS: The mean pulsatility index fell to 53% of its pretreatment value within 12 days E2 administration (P < or = 0.0001) and was 66% of its pretreatment value in the combined phase (P < 0.005). Similar changes were seen in cycle 2. Time since menopause was correlated with the pretreatment pulsatility index (r = 0.674, P < 0.05) and change in pulsatility index on treatment (r = 0.856, P < 0.001). CONCLUSION: Gonadal hormones have a profound effect on arterial tone in postmenopausal women; this action may help explain some of the beneficial effects of estrogen on arterial disease risk.

Administration, Cutaneous↗
PubMed1992

HRT: developments in therapy.

Various forms of oestrogen have been available for use as Hormone Replacement Therapy (HRT) for approximately 50 years. However, there has been little change in the mode of administration until the last 10-15 years. Although the oral route has remained the mainstay of therapy, non-oral routes of administration have been developed. During the 1970s it became clear that use of unopposed oestrogens in women with an intact uterus resulted in an increase in risk of endometrial carcinoma and thus the current practice of adding a sequential progestogen each month, to prevent endometrial hyperplasia, was introduced. However, certain progestogens can cause side-effects and some of the metabolic changes which they induce are potentially undesirable. Thus the search continues for new oral progestogens which are more 'metabolically friendly' than those in current use. Additionally, non-oral delivery systems for progestogens have been studied, such as the transdermal route (patches) and local administration within the uterine cavity (progestogen-containing intra-uterine devices). Both these strategies may minimise their symptomatic, psychological and metabolic effects. Continuous (every day) administration of progestogens in combination with the oestrogen, or the use of new compounds (e.g. tibolone) may overcome the problem of regular withdrawal bleeding which some women find unacceptable. However, it remains to be determined whether such therapies are as efficacious as conventional oestrogen/sequential progesterone regimens.

Administration, Cutaneous↗
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↗