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Biomedical subjects

M I Whitehead

Publications and source records attributed to M I Whitehead.

At least 37 records · Page 2Linked to original sources
PubMed1994

Long-term effects of oral and transdermal hormone replacement therapies on serum lipid and lipoprotein concentrations.

OBJECTIVE: To see whether the short-term changes in serum lipid and lipoprotein concentrations induced by postmenopausal estrogen-progestin therapy are maintained in the long term. METHODS: Sixty-one healthy postmenopausal women were randomized to either oral therapy (continuous conjugated equine estrogens at 0.625 mg/day with sequential dl-norgestrel at 0.15 mg/day for 12 days each cycle) or transdermal therapy (patches delivering continuous 17 beta-estradiol [E2] at 0.05 mg/day with sequential norethindrone acetate at 0.25 mg/day for 14 days each cycle). Twenty-nine healthy postmenopausal women who did not request therapy served as a reference group. Fasting serum lipid and lipoprotein concentrations were monitored for 3 years. RESULTS: Studied in the estrogen-progestin phase, oral and transdermal therapies reduced serum total cholesterol concentrations by 12.1% (P < .001) and 8.4% (P < .001), respectively, and those of low-density lipoprotein (LDL) by 14.2% (P < .001) and 6.6% (P < .01), respectively. These changes, apparent at 3 months, were maintained over 3 years. Serum triglyceride concentrations fell by 2.5% (P < .05) and 16.4% (P < .01), respectively. These decreases were evident after 6 months in both groups but were maintained over 3 years only in the transdermal group. High-density lipoprotein (HDL) concentrations fell in women given oral therapy (7.8%, P < .05) and transdermal therapy (10.7%, P < .001), as well as in untreated women (7.0%, P < .05). CONCLUSIONS: The potentially beneficial effects of estrogen-progestin therapy on serum total and LDL cholesterol and on triglycerides were maintained over 3 years. Interpretation of the potentially detrimental effects on HDL concentrations was hindered by the changes seen in untreated women.

Administration, Cutaneous↗
PubMed1994

Effect of continuous combined estrogen and desogestrel hormone replacement therapy on serum lipids and lipoproteins.

OBJECTIVE: To determine the effects of continuous combined hormone replacement therapy with desogestrel and 17 beta-estradiol (E2) on serum lipids and lipoproteins. METHODS: Fifty-seven healthy postmenopausal women of less than 60 years of age were studied prospectively and treated with oral desogestrel 0.15 mg/day and micronized 17 beta-E2 1 mg/day, both taken continuously. Fasting venous blood samples for serum lipids and lipoproteins were taken before and after 6 and 12 months of treatment. RESULTS: Thirty-two women completed the study. Levels of all serum lipids and lipoproteins fell significantly by 6 months and remained low at 12 months. The mean percentage reduction after 12 months of treatment was 12.8% for high-density lipoprotein (HDL) cholesterol, which largely resulted from a reduction in the HDL2 subfraction, which fell by 25.7%. The mean percentage reduction for both low-density lipoprotein (LDL) cholesterol and triglycerides was 7.7%. The median percentage reduction for lipoprotein (a) was 17.6%. CONCLUSIONS: This combination of hormone replacement therapy had profound effects on serum lipids and lipoproteins. According to current concepts, reductions in total and LDL cholesterol, triglycerides, and lipoprotein (a) may reduce cardiovascular disease risk. The reduction in HDL was unexpected, given the rise in HDL that has been demonstrated when desogestrel is combined with ethinyl estradiol in the contraceptive pill. The lowering of HDL observed in this study is undesirable and may be potentially harmful. Our results indicate that when desogestrel 0.15 mg/day is combined with micronized 17 beta-E2 1 mg/day in a continuous manner, the effects of the progestogen on HDL predominate and cause a reduction in HDL and the HDL2 subfraction.

Cholesterol, HDL↗
PubMed1993

Psychological impact of screening for familial ovarian cancer.

BACKGROUND: Psychological distress following false-positive results could constitute a substantial disadvantage of cancer screening. PURPOSE: The purpose of this prospective study was to evaluate the psychological impact of true-negative and false-positive results in a high-risk group of women in a screening program to detect early familial ovarian cancer by ovarian ultrasound scan. The influence of coping style was also assessed. METHODS: Of 500 women who contacted the nationally advertised screening program, 302 received the scan and participated in the study. Before the screening, they were mailed a questionnaire concerning psychological state, coping style, and anxiety about risk of cancer. Transabdominal ultrasonography and transvaginal ultrasonography with color Doppler imaging were used to detect persistent ovarian lesions and changes in volume. Women were informed of any abnormality immediately and asked to return for another scan after 6 weeks. Those with a persistent ovarian mass were referred for hysterectomy and bilateral oophorectomy. The questionnaire was used to reassess psychological distress after the first ultrasound scan, after re-scanning, and after surgery. RESULTS: The first scan showed negative results for 233 of the 302 women; 69 (23%) had abnormalities in ovarian morphology. Sixty-four of the 69 had a second scan, with negative results for 32 and equivocal results for 12; 20 had surgery because the results of both scans were positive. None of the patients in the screening program were found to have ovarian cancer. After the first scan, psychological distress and worries about cancer were significantly reduced (P < .001) in the women who had negative results. Responses to positive results depended on the baseline coping style and the clinician's appraisal of malignancy potential at the time of the scan. Women who had information-seeking coping styles and those who were referred for surgery had higher levels of distress than other women. At follow-up, the anxiety scores of women who had positive results on both scans but negative results at surgery had returned to baseline levels. CONCLUSIONS: The findings suggest that false-positive results in screening are associated with increased distress in the short term, but these adverse effects do not appear to be severe or persistent. Women who had surgery appeared to welcome the certainty that they could never develop ovarian cancer. IMPLICATIONS: The issue of continued surveillance needs to be addressed, since many women expressed the desire to have the scan repeated regularly.

Adult↗
PubMed1993

Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging.

OBJECTIVE: To assess the value of transvaginal ultrasonography with colour blood flow imaging in detecting early ovarian cancer in women with a family history of the disease. DESIGN: Study of self referred symptomless women with a close relative who had developed the disease. Each woman was screened to detect persistent lesions and defined changes in ovarian volume. Morphological score and pulsatility index were recorded. SETTING: Ovarian screening clinic. SUBJECTS: 1601 self referred women. INTERVENTIONS: Women with a positive screening result were recommended to have further investigations. MAIN OUTCOME MEASURES: Findings at surgery and histology of abnormal ovaries. Morphological score > or = 5 and pulsatility index < 1.0 at last scan. RESULTS: Women were aged 17 to 79 (mean 47) years; 959 (60%) were premenopausal, 469 (29%) were naturally postmenopausal, and 173 (11%) had had a hysterectomy. 157 women had a pedigree suggestive of the site specific ovarian cancer syndrome and 288 of multiple site cancers. 61 women had a positive screening result (3.8%, 95% confidence interval 2.9 to 4.9%), six of whom had primary ovarian cancer detected at surgery (five stage Ia, one stage III). Use of a high morphological score or a low pulsatility index increased the odds of finding ovarian cancer from 1:9 to about 2:5 (1:1 in the highest risk groups). Five interval cancers were reported (three ovarian and two peritoneal). Eight of the 11 cancers developed in women with pedigrees suggestive of inherited cancer. CONCLUSIONS: Transvaginal ultrasonography with colour flow imaging can effectively detect early ovarian cancer in women with a family history of the disease. The screening interval should be less than two years.

Adolescent↗
PubMed1993

Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy.

Estrogen/progestin steroid combinations adversely affect glucose tolerance and insulin resistance, but their effects in combined hormone replacement therapy (HRT) have rarely been evaluated. We studied 61 untreated symptomatic postmenopausal women randomized to receive oral (conjugated equine estrogens, 0.625 mg/d continuous + levonorgestrel, 0.075 mg/d for 12 days of each 28-day cycle) or transdermal therapy (estradiol 17 beta, 0.05 mg/d continuous + norethindrone acetate, 0.25 mg/d for 14 days of each 28-day cycle). An untreated control group of 30 postmenopausal women not seeking HRT was also studied. Intravenous glucose tolerance tests (IVGTT) were performed at baseline and 3, 6, and 18 months later. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. There were no changes in glucose or insulin concentrations with transdermal therapy. Oral therapy caused a deterioration of glucose tolerance and an increased overall plasma insulin response, apparently due to a reduction in the immediate plasma insulin response to glucose. This may have resulted from increased hepatic insulin uptake, uncompensated for by an increase in first-phase pancreatic insulin secretion. Neither treatment caused significant insulin resistance compared with baseline, but with the oral treatment insulin resistance was greater during the combined phase compared with the estrogen-only phase. Thus the oral regimen affected both insulin delivery and insulin resistance. The transdermal regimen had relatively few effects on insulin metabolism.

Administration, Cutaneous↗
PubMed1993

The practicalities of hormone replacement therapy.

An appropriate regimen of HRT using oestrogen with or without progestogen can be found for the majority of patients. In many cases this will be the first or second therapy that is chosen and for most women will be one of the combination packs that are commercially available. In a significant number of patients, however, these formulations will either not control symptoms or bleeding or will cause unacceptable progestogenic side-effects. Separate prescribing of oestrogen and progestogen will then be required. We suspect that the reported low compliance of women taking HRT in the general population may be related to the deficiencies of the available combination packs and reluctance of physicians to separately prescribe the oestrogen and progestogen components of HRT. The latter is understandable as the literature contains so few guidelines concerning prescribing. It is hoped that progestogens that have less side-effects than the C-19 steroids (currently universally used in combination packs of HRT) will be incorporated into new formulations. The option of prescribing oestrogens to non-hysterectomized women in the form of continuous combined therapy is not available to many physicians because the necessary endometrial sampling every 12-18 months cannot be arranged; the current outpatient methods of sampling require experience of manipulation of instruments within the uterine cavity that is usually only acquired during gynaecological training. There are still many uncertainties about the appropriate combination of oestrogen and progestogen that should be incorporated into a continuous combined regimen to avoid the troublesome bleeding that occurs in a significant proportion of women when starting this therapy. Many previous studies were seriously flawed and further research, carefully designed and conducted, is urgently needed.

Drug Therapy, Combination↗
PubMed1993

Postmenopausal bone loss: does HRT always work?

In a 3-year study comparing oral and transdermal HRT, we measured bone density in the spine and proximal femur by dual-photon absorptiometry. Sixty-six women were randomly allocated to receive either oral conjugated equine oestrogens, 0.625 mg daily, together with cyclical oral dl-norgestrel, 0.15 mg daily, or transdermal 17 beta-oestradiol, 0.05 mg daily, together with cyclical transdermal norethisterone acetate, 0.25 mg daily. We found that only 2% showed significant vertebral bone loss on either treatment, whilst approximately 12% lost from the proximal femur. Compliance was demonstrated by monitoring all used patches and pill packets, recording all side effects and bleeding patterns, and by the demonstration of appropriate changes in levels of gonadal steroids and lipoproteins. Comparing the bone losers with the ten highest gainers, lowers were closer to their menopause but were not different in body mass or life style. Serum oestradiol levels were similar, and both groups showed a similar response in terms of changes in bone biochemical markers and lipoproteins in response to HRT. In thus seems that a small proportion of women do not conserve bone density in the proximal femur with standard doses of HRT. It remains to be determined whether they could be identified by more specific biochemical markers of bone turnover, and whether they would maintain with a higher dose of oestrogen.

Administration, Cutaneous↗
PubMed1993

Oral versus transdermal hormone replacement therapy.

Loss of ovarian function at the menopause results in an increased risk for cardiovascular disease and osteoporosis. Hormone replacement therapy (HRT) in postmenopausal women may reduce or remove this increased risk. The high hepatic bolus seen with oral steroid administration, which may produce unwanted metabolic effects, is avoided by transdermal administration. We studied the metabolic effects of transdermal HRT in comparison with oral HRT or no treatment in 96 healthy postmenopausal women over 3 years. Treatment consisted of either continuous oral conjugated equine estrogens, 0.625 mg daily, with sequential oral dl-norgestrel, 0.15 mg daily, for 12 days per month or continuous transdermal estradiol-17 beta, 0.05 mg daily, with sequential transdermal norethindrone acetate, 0.25 mg daily, for 14 days per month. We measured bone biochemistry and density, serum lipids, lipoproteins and apolipoproteins, and glucose, insulin, and C-peptide concentrations following an intravenous glucose bolus. Minimal modelling analyses provided measures of glucose and insulin kinetics. Both HRT regimens were effective in preventing bone loss, and produced generally favourable lipid and lipoprotein changes. Progestin addition prevented increases in HDL2 cholesterol, but lowered triglycerides. Transdermal estrogen lowered triglycerides, whereas oral estrogen increased them. Furthermore, oral HRT resulted in a deterioration in glucose tolerance and an overall increase in insulin secretion. Transdermal HRT appears at least as effective as oral HRT in preventing postmenopausal osteoporosis, and produces as good, if not better, changes in metabolic risk markers for cardiovascular disease.

Administration, Cutaneous↗
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↗