David W Purdie

Bone histology and mineral homeostasis in human pregnancy

Summary. Mineral homeostasis was studied biochemically and histologically in patients in early pregnancy and at term. In early pregnancy there was evidence of increased and reversible resorption of bone, whereas in late pregnancy bone demonstrated active formation and rapid mineralization with minimal resorption. Gut absorption of calcium was not increased in early pregnancy. The overall findings were consistent with calcium liberation from bone in early pregnancy, and with enhanced conservation of bone calcium at term. It is proposed that the additional calcium required during pregnancy is derived largely from the skeleton during early gestation and from dietary absorption at term.

Prevalence of Osteoporosis and Related Risk Factors in UK Women in the Seventh Decade: Osteoporosis Case Finding by Clinical Referral Criteria or Predictive Model?

Abstract: The objectives of the study were: to determine the prevalence of osteoporosis in women in their seventh decade; to determine the number of women who conformed to at least one of the current East Yorkshire Clinical Referral Criteria for Osteoporosis; and to determine the sensitivity and specificity of these referral criteria in the diagnosis of osteoporosis and to compare this with the receiver operating characteristic (ROC) curve of a logistic regression model incorporating variables that were significantly associated with the risk of osteoporosis. An observational study was carried out at the Centre for Metabolic Bone Disease, Hull Royal Infirmary, on women in their seventh decade from three general practices. Densitometric assessment of lumbar spine and femoral neck was carried out using dual-energy X-ray absorptiometry (DXA) and a detailed medical history taken. The main outcome measures were prevalence of osteoporosis in women in their seventh decade and efficacy of agreed clinical referral criteria at osteoporosis case finding. Of 823 Caucasian women who underwent DXA, 24% proved to have osteoporosis at hip, spine or both according to WHO criteria. A further 49% had osteopenia detected at hip, spine or both. At least one of the referral criteria was present in 47% of the women assessed. The sensitivity of the clinical referral criteria for detection of osteoporosis was 58% with a corresponding specificity of 60%. This point lies below the ROC curve (area under fitted curve, Az= 0.73) of a logistic regression model incorporating weight, age at menopause and current use of hormone replacement therapy. In conclusion, osteoporosis according to WHO criteria was found in almost 25% of women in their seventh decade. A simple logistic regression model provided a more sensitive method of osteoporosis case finding than the selective screening component of the clinical referral criteria employed in our practice.

Effects of sex steroids on sleep

Sex steroid secretions are generally synchronous with the circadian rhythm and sleep, and there is evidence that prolactin secretion is sleep-dependent. Polysomnographically assessed changes in sleep during the menstrual cycle are characterized by increased EEG activity in the 14-15-Hz (sleep spindle) range in the luteal phase accompanying an increase in core temperature. There are no other consistent changes in sleep architecture associated with the menstrual cycle. The hot sweats which disturb sleep in menopausal women are attributable to oestrogen deficiency and are reduced by oestrogen replacement therapy. Although it is often assumed that the psychological changes during the menopause are attributable to chronic sleep disturbance caused by hot sweats, the evidence for this is uncertain. Sex steroids have also been shown to have a role in the aetiology of obstructive sleep apnoea and its treatment. It is clear that the sex steroids are all implicated in sleep and thermoregulatory processes, although we cannot as yet define their precise roles.

Effects of estrogens and hormone replacement therapy on breast cancer risk and on efficacy of breast cancer therapies

This review summarises preclinical and clinical data on effects of endogenous and exogenous estrogens on probability of breast cancer diagnosis, and on the course and efficacy of breast cancer therapies. The data indicate that higher endogenous estrogen exposure (e.g. pregnancy, early menarche and late menopause, estrogen levels in future breast cancer patients, obesity) or exogenous estrogens (oral contraceptives; hormone replacement therapies) may be associated with an increased probability of breast cancer diagnosis. However, there is little evidence that estrogens have deleterious effects on the course of breast cancer. Moreover, increased incidence of breast cancer diagnosis after prolonged hormone replacement therapy (HRT) use seems to be associated with clinically less advanced disease. In studies assessing both diagnosis and mortality, HRT is frequently associated with reduced mortality compared to never users. The interaction of progestagens and estrogens on the probability of breast cancer diagnosis is complex and dependent on type of progestagens and regimens employed. Efficacy of current treatment modalities for breast cancer (surgery, irradiation, adjuvant therapy or chemotherapy) is not negatively influenced by estrogens at concentrations considerably higher than those attained with current HRT preparations. Although it cannot be excluded that estrogens increase the probability of breast cancer diagnosis, available data fail to demonstrate that, once breast cancer has been diagnosed, estrogens worsen prognosis, accelerate the course of the disease, reduce survival or interfere with the management of breast cancer. It may therefore be concluded that the prevalent opinion that estrogens and estrogen treatment are deleterious for breast cancer, needs to be revisited. However, results of ongoing prospective, randomised clinical trials with different HRT regimens in healthy women or breast cancer survivors are needed to provide more definite conclusions about risks and benefits of HRT.

The effect of long term oestradiol implantation on bone mineral density in postmenopausal women who have undergone hysterectomy and bilateral oophorectomy

Twelve women who had received oestradiol implantation on demand for at least 15 years following hysterectomy with bilateral oophorectomy, underwent bone densitometry of hip and spine. Bone mass of hip and spine was significantly elevated above that of both the age matched mean to a degree hitherto undocumented. This suggests that oestrogen in high doses or over a long period may produce a true anabolic effect on bone mass.

Influence of birth weight on adult bone mineral density

Bone mineral density (BMD) increases during growth until a peak is reached at maturity. The risk of development of postmenopausal osteoporosis depends on the peak bone density and the rate of its subsequent loss. To identify whether low weight at birth could affect the peak bone density, we measured BMD at both the lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA) in a group of women who had low weight at birth and in a control group of normal birth weight. There was no significant correlation between the weight at birth and the adult BMD. It appears, therefore, that low weight at birth does not influence the peak bone density and that prematurity is not a risk factor for osteoporosis.

Prevention of postmenopausal bone loss at lumbar spine and upper femur with tibolone: a two‐year randomised controlled trial

Objective To examine the effects of tibolone on bone mineral density and its concurrent safety and subject acceptability.

Changes in trabecular bone architecture in women during pregnancy

Objective To examine the effect of early and late pregnancy on the microarchitecture of maternal cancellous bone.

Gabapentin for the management of hot flushes: a case series.

ObjectiveTo audit the effectiveness of the anticonvulsant gabapentin on hot flushes in postmenopausal women. DesignThis was an open case series involving 11 postmenopausal women who were willing to take gabapentin for the relief of their hot flushes and were willing to keep a diary recording the number and intensity of their hot flushes, both before and during treatment. Gabapentin was started at a dose of 300 mg, to be taken at night, and the women were instructed to increase the dose up to 1,200 mg, according to symptom behavior. ResultsEleven women agreed to participate for on average 53.22 days (range, 2–79 days), but two discontinued participation—one before starting treatment and one after 2 days—so there are complete data sets for nine women. Gabapentin was found to be extremely effective in reducing hot flush activity (P < 0.001;Fig. 1). A significant reduction in symptoms was observed with a dose of 300 mg/day (P < 0.001). Scores on the Green Climacteric Scale were significantly improved from a mean of 25.72 (range, 12–42) to 19.25 (range, 13–31; P < 0.001). Palpitations (P = 0.001), panic attacks (P = 0.0001), mood (P = 0.023), muscle and joint pains (P = 0.021), and paresthesias and loss of sensation in the extremities (P = 0.001) were also shown to improve with treatment. ConclusionsIn the present case series, gabapentin was well tolerated and could be a valuable alternative for the treatment of hot flushes in women with contraindications to hormonal replacement therapy. It would be particularly beneficial for women in whom aches and pains and paresthesias are also a significant feature of the climacteric syndrome.

The relation between bone mineral density and early pregnancy loss

Objective To determine if women who suffer from early pregnancy loss are at increased risk of osteoporosis later in life.