Tord Naessen

The risk of acute myocardial infarction after oestrogen and oestrogen‐progestogen replacement

Objective To determine the relative risk of developing a first acute myocardial infarction after treatment with oestrogens alone or oestrogen‐progestogen combinations.

Fracture of the distal forearm as a forecaster of subsequent hip fracture: a population-based cohort study with 24 years of follow-up.

SummaryObjective: To determine the long-term risk of hip fracture following fracture of the distal forearm. Design: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. Fracture cohort: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period. 1968–1972, in all 1,126 women and 212 men. Control cohort: An equal number of population-based, age-and sex-matched control persons selected from a population register. Measurements: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. Results: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. Conclusions: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered.

Hormone Replacement Therapy and the Risk for First Hip Fracture: A Prospective, Population-based Cohort Study

OBJECTIVE To determine the relative risk for sustaining a first hip fracture after hormone replacement therapy. DESIGN Prospective population-based cohort study with an average observation period of 5.7 years. SETTING A prescription-based cohort in the Uppsala health care region in Sweden. PARTICIPANTS The cohort (23 246 women) comprised virtually all women of 35 years of age and older who received noncontraceptive estrogens from April 1977 through March 1980. Comparisons were made with women in the background population. MEASUREMENTS Follow-up through 1983 was done with regard to hospital admissions for a first cervical or trochanteric hip fracture. The observed number of cases was compared with that expected on the basis of person-years of observation in the cohort and incidence rates in the background population. Analyses were made in exposure categories, based solely on prescription data. MAIN RESULTS During 133 022 person-years of observation, 163 cases of first hip fracture occurred, compared with the 205.5 expected, yielding an overall relative risk of 0.79 (95% CI, 0.68 to 0.93). The greatest protective effect (relative risk, 0.37; CI, 0.13 to 0.79) was found against trochanteric fracture among women receiving potent estrogens who were under 60 years of age at cohort entry. This group also had the highest proportion of treatments with combinations of estrogens and progestogen (41%). Treatment with less potent estrogens, mainly estriols, had no protective effect. Data indicated that the baseline risk for hip fracture was not lower in the cohort women than in the background population. CONCLUSIONS Treatment with potent estrogens, both alone and possibly when combined with progestogens, reduces the risk for both cervical and trochanteric hip fractures within the first decade after menopause.

Breast cancer risk associated with gynecologic surgery and indications for such surgery

Risk of breast cancer was assessed in relationship to gynecologic operations using data from a record‐linkage study involving 15,844 women in the Uppsala Health Care Region of Sweden, who underwent surgery between 1965 and 1983. Data abstracted from medical records for the breast cancer cases and a random sample of the cohort allowed examination of risk associated with these operations in regard to menopausal status and indications for the operations. Among women who were pre‐menopausal at the time of operation, a bilateral oophorectomy before the age of 50 years was associated with a 50% reduction in the risk of breast cancer compared with the background population, a reduction in risk evident within 10 years of the operation. A bilateral oophorectomy after the age of 50 years in pre‐menopausal women or after a natural menopause was not associated with any reduction in risk. There were no reductions in risk associated with a unilateral oophorectomy or hysterectomy among women who were pre‐menopausal at the time of operation. In fact, hysterectomy alone was associated with a slight increase in breast cancer risk when the operation was due to myomas, abnormal bleeding, and, possibly, severe forms of endometriosis but not to other reasons. Risk did not vary substantially by indications for oophorectomy, including benign ovarian neoplasms and functional ovarian cysts, though endometriosis was associated with a non‐significant increase in breast cancer risk. Int. J. Cancer, 70:150–154, 1997.

Postmenopausal hormone therapy and risk of cardiovascular disease and hip fracture in a cohort of Swedish women.

Postmenopausal estrogen use is associated with a reduced risk of heart disease and hip fracture; in observational studies, different behaviors among hormone users and nonusers may partially explain these results. We examined risk of cardiovascular disease and hip fracture with medium-potency compared with low-potency or short-term estrogen use, and the effect of added progestin, among 9,236 women in Uppsala, Sweden, who responded to a mailed questionnaire in 1987-1988. Using population registries, we identified 213 cases of myocardial infarction, 289 strokes, and 114 hip fractures from 1987-1995. We found a reduced risk of myocardial infarction for medium-potency compared with low-potency or short-term estrogen use (relative risk = 0.75, 95% confidence interval (CI) = 0.56-0.99), with a similar decrease in the subgroup that took estrogens with progestin (RR = 0.69, 95% CI = 0.45-0.90). There was no relation of medium-potency estrogen to stroke (RR = 0.91, 95% CI = 0.71-1.17, and RR = 0.81, 95% CI = 0.61-1.10 for the subgroup taking progestin), and no effect of duration on either heart disease or stroke. We observed a reduction in hip fractures for medium-potency use (RR = 0.65, 95% CI = 0.45-0.95), and for use of combined estrogen-progestin therapy (RR = 0.64, 95% CI = 0.41-1.00). These data support a decreased risk of heart disease and hip fracture for medium-potency estrogen use alone or with progestin; self-selection to hormone use cannot explain these reductions.

Better postural balance in elderly women receiving estrogens

OBJECTIVE The amount of bone mass and the tendency to fall are main risk factors for hip fractures and both deteriorate with advancing age. The dynamics between estrogen exposure and fracture protection seem too rapid to be explained by an effect on bone mass only. Postural balance function may be another potential mechanism for the fracture-protecting effect of estrogens. STUDY DESIGN We examined 16 long-term users of 17 beta-estradiol implants (20 mg) (mean age 67.9 years and mean duration of treatment 17.3 years [3.3 to 34 years]) and 16 age-matched (+/-2 years) nonusers (mean age 68.3 years). Postural balance (sway velocity) was measured by static posturography before and after blindfolding and application of vibration stimulus (20 to 100 Hz) to the calf muscles to disturb the proprioception and to induce imbalance. RESULTS Sway velocities were significantly lower in estrogen users than in nonusers (p = 0.0067) and similar to those in young premenopausal women. The differences were accentuated after provocation by blindfolding and by increasing frequencies of vibration stimulus to the calf muscle. Serum levels of estradiol and estradiol/sex hormone-binding globulin were negatively and follicle-stimulating hormone levels positively associated with sway velocity (p = 0.0194, p = 0.0036, and p = 0.0052, respectively) and independent of age (p = 0.02 to 0.005), supporting causality between estrogen exposure and postural balance. CONCLUSIONS These data indicate that postural balance function is better preserved in long-term estrogen users than in nonusers. Effects on postural balance function may be one mechanism explaining the rapid increase in distal forearm fractures early after menopause and the rapid dynamics between estrogen exposure and hip fracture protection and may potentially reduce the fracture risk in elderly women starting estrogen replacement therapy in spite of marginal increases in bone mass.

Risk of myocardial infarction after oophorectomy and hysterectomy

To determine the risk of developing a first myocardial infarction after a hysterectomy and/or oophorectomy. Case-cohort analysis performed among 17,126 women in the Uppsala Health Care Region of Sweden, who had undergone a hysterectomy and/or oophorectomy in 1965 to 1983. Record linkage was used for follow-up and medical records to ascertain the actual history of oophorectomy. Risk estimates were calculated by relating the observed number of cases in the cohort to that expected on the basis of incidence rates in the population. Overall, 214 cases of myocardial infarction were observed. In premenopausal women a bilateral oophorectomy alone tended to increase the relative risk 1.6; 95% CI 0.8-3.1, but this operation combined with hysterectomy increased the risk only among those aged 50 and over at surgery. Hysterectomy at premenopausal age or unilateral oophorectomy did not alter the risk of myocardial infarction. In naturally menopausal women, hysterectomy-mainly for uterine myoma-was associated with a four-fold increase in relative risk (3.8; 95% CI 1.9-7.8). Hysterectomy for treatment of myoma performed after a natural menopause is linked to an excess risk for myocardial infarction. Bilateral oophorectomy before menopause may increase the risk of myocardial infarction.

Reduced risk of breast and endometrial cancer among women with hip fractures (Sweden)

To test the hypothesis that osteoporosis, which results partly from long-term estrogen deficiency, is associated with a lowered risk of breast and endometrial cancer, a population-based cohort study was performed in Sweden. Some 18,000 women were followed through record-linkages after a first hip fracture, on average for almost six years, to ascertain the incidence of breast and endometrial cancer. Expected numbers were derived from the general population. Overall, 253 cases of breast cancer were observedcf 300 expected (standardized incidence ratio [SIR]=0.84; 95 percent confidence interval [CI]=0.74–0.95). Forty-eight cases of endometrial cancer were foundcf 55 expected (SIR=0.87, CI=0.54–1.16). There was no clearcut pattern of breast cancer risk by age at diagnosis of hip fracture, follow-up time, or calendar period. Our results are consistent with thea priori hypothesis that long-term estrogen deficiency is associated with a reduced risk of developing breast cancer as well as endometrial cancer.

Menopausal symptoms and quality of life during the menopausal transition in Sri Lankan women.

Objective: To assess the prevalence of menopausal symptoms in a population of Sri Lankan women and the relationship with their health-related quality of life. Design: A community-based, cross-sectional study was conducted on 683 women ages 45 to 60 years living in the district of Colombo, Sri Lanka. A cluster sampling method was used for recruitment of the sample. Information was collected on demographic, socioeconomic, menstrual, and reproductive history using structured interviews. The Menopause Rating Scale was used to assess menopausal symptoms and the Short Form 36 health survey was used to assess the health-related quality of life. Results: Of the sample, 59.4% were postmenopausal and 18.4% were perimenopausal; 90% of the sample had one or more menopausal symptoms. The most prevalent menopausal symptoms were joint and muscular discomfort (74.7%), physical and mental exhaustion (53.9%), and hot flushes (39.1%). Hot flushes, sleep problems, and joint/muscular discomfort showed an increase in prevalence from the premenopausal category to the postmenopausal category (P < 0.05 for all). Chronic illness in the women was significantly associated with the presence of menopausal symptoms (P < 0.01). Women with menopausal symptoms had significantly lower (P < 0.05) quality-of-life scores in most of the domains of the Short Form 36 compared with women without symptoms. Conclusions: The majority of these Sri Lankan women reported one or more menopausal symptom. Chronic illness was significantly associated with these symptoms. The presence of menopausal symptoms was significantly associated with a decreased health-related quality of life in the women.

SKELETAL RESPONSIVENESS TO PARATHYROID HORMONE IN HEALTHY FEMALES : RELATIONSHIP TO MENOPAUSE AND OESTROGEN REPLACEMENT

In order to directly evaluate the role of parathyroid hormone (PTH) and Its Interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1–38) PTH was Infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical Indices of bone turnover: serum osteocalcin and alkallne phosphatase and fasting urinary hydroxyproline and calcium.