Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss.

Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status.

Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction.

Low bone mineral density (BMD) is a major risk factor for development of osteoporosis; increasing evidence suggests that attainment and maintenance of peak bone mass as well as bone turnover and bone loss have strong genetic determinants. We examined the association of BMD levels and their change over a 3-year period, and polymorphisms of the estrogen receptor (ER), vitamin D receptor (VDR), type I collagen, osteonectin, osteopontin, and osteocalcin genes in pre- and perimenopausal women who were part of the Michigan Bone Health Study, a population-based longitudinal study of BMD. Body composition measurements, reproductive hormone profiles, bone-related serum protein measurements, and life-style characteristics were also available on each woman. Based on evaluation of women, ER genotypes (identified by PvuII [n = 253] and XbaI [n = 248]) were significantly predictive of both lumbar spine (p < 0.05) and total body BMD level, but not their change over the 3-year period examined. The VDR BsmI restriction fragment length polymorphism was not associated with baseline BMD, change in BMD over time, or any of the bone-related serum and body composition measurements in the 372 women in whom it was evaluated. Likewise, none of the other polymorphic markers was associated with BMD measurements. However, we identified a significant gene x gene interaction effect (p < 0.05) for the VDR locus and PvuII (p < 0.005) and XbaI (p < 0.05) polymorphisms, which impacted BMD levels. Women who had the (-/-) PvuII ER and bb VDR genotype combination had a very high average BMD, while individuals with the (-/-) PvuII ER and BB VDR genotype had significantly lower BMD levels. This contrast was not explained by differences in serum levels of osteocalcin, parathyroid hormone, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D. These data suggest that genetic variation at the ER locus, singly and in relation to the vitamin D receptor gene, influences attainment and maintenance of peak bone mass in younger women, which in turn may render some individuals more susceptible to osteoporosis than others.

Magnitude and variability of sequential estradiol and progesterone concentrations in women using depot medroxyprogesterone acetate for contraception.

OBJECTIVE: To describe the magnitude and variability of sequential serum estradiol and progesterone concentrations throughout one depot medroxyprogesterone (DMPA) injection interval. DESIGN: Prospective study. SETTING: Family planning and women's health clinics. PATIENT(S): Thirty-one women, ages 19 to 46, using DMPA for contraception. INTERVENTION(S): Serum for estrogen and progesterone was collected weekly throughout one DMPA injection interval. MAIN OUTCOME MEASURE(S): Serum estradiol and progesterone concentrations; estradiol patterns produced from data plotted across the entire DMPA injection interval. RESULT(S): The average daily estradiol concentrations ranged from 7.9 to 69.1 pg/mL, with a mean of 18.9 +/- 12.9 and a median of 15.4 pg/mL. Average daily progesterone concentrations ranged from 0.14 to 1.1 ng/mL, with a mean of 0.40 +/- 0.19 ng/mL and a median of 0.36 ng/mL. Two general patterns of estradiol concentrations were identified. One pattern, observed in approximately one third of the participants, reflected estradiol concentrations that were extremely low (mean, 12.7 +/- 3.6 pg/mL; median, 13.4 pg/mL) and consistently flat across the DMPA injection interval. The second pattern, seen in the remaining participants, reflected estradiol concentrations that were higher (mean, 22.2 +/- 14.9 pg/mL; median, 17.3 pg/mL) and quite variable. CONCLUSION(S): This study demonstrated that estradiol concentrations were lower than the 40 to 50 pg/mL reported in most studies and, for the majority of women, varied substantially across the DMPA injection interval.

Occupational exposures and risk of female infertility.

This study examined the association between occupational chemical and radiation exposures and risk of medically diagnosed infertility in 281 women compared with 216 fertile women. After adjustment for age and exposures that occurred before case/referent ascertainment, there was an increased risk of infertility among those women exposed to volatile organic solvents (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.11 to 2.71), chemical dusts (OR, 2.66; CI, 1.17 to 6.05), pesticides (OR, 3.02; CI, 1.10 to 8.29), and video display terminals (OR, 2.21, CI, 1.22, to 4.01). Among the medically diagnosed causes of infertility, the adjusted risk associated with having an ovulatory factor increased among those women exposed to solvents (OR, 1.75; CI, 1.03 to 2.98), dusts (OR, 3.00; CI, 1.19 to 7.52), or pesticides (OR, 3.82; 1.28 to 11.42). Solvents and dusts also were associated with a higher risk of tubal-factor infertility (solvents; OR, 1.95; CI, 1.08 to 3.52; dusts: OR, 2.87; CI, 1.05 to 7.88) and endometriosis (solvents: OR, 2.13; CI, 0.96 to 4.72; dusts: OR, 3.63; CI, 0.99 to 13.28). Video display terminal exposure was more likely to be found among those women diagnosed with endometriosis (OR, 3.69; CI, 1.50 to 9.13) and cervical-factor infertility (OR, 2.65; CI, 0.99 to 7.12). Results suggest that among women with a medically confirmed diagnosis, fertility may be adversely affected by a variety of occupational chemical exposures.

Identifying undiagnosed rheumatic disorders among patients with TMD.

If a patient with TMD has a coexisting rheumatic disorder, it may adversely affect the TMD symptoms and treatment outcome. A clinic that specializes in TMD treatment asked symptom-related questions of 104 patients with TMD, and a rheumatology clinic then performed rheumatologic evaluations. The authors review the results of the rheumatologic evaluations and the predictive probability for the questions. The findings of this study suggest questions that practitioners can ask to help identify patients with TMD who have a high probability of being diagnosed with a coexisting rheumatic disorder.

Weight, fat mass, and central distribution of fat increase when women use depot-medroxyprogesterone acetate for contraception.

OBJECTIVE: To compare longitudinal changes in weight, body fat, and ratio of central to peripheral fat mass among first-time depot-medroxyprogesterone acetate (DMPA) users to women using no hormonal contraception, and to evaluate user characteristics associated with that change. DESIGN: Prospective longitudinal study. SUBJECTS: Healthy women, aged 18-35 y, using DMPA for contraception (n=178) and women using no hormonal contraception (n=145). MEASUREMENTS: Weight, body fat, and the central distribution of fat, measured at 3-month intervals for 30 months, by electronic scale and dual-energy X-ray absorptiometry (DEXA). The ratio of central to peripheral distribution of body fat was computed by dividing the body fat in the conventional DEXA trunk region of interest (ROI) by the ROI's that encompass the arms, hips and legs. RESULTS: Women using DMPA had a significantly greater increase in all measures of fatness than women using no hormonal method of contraception (P<0.03). The observed weight of DMPA users increased from a mean of 69.4 kg (s.d.=16.9) at baseline to 75.5 kg (s.d.=25.0) at 30 months; an increase of 6.1 kg (8.8.%). Fat mass increased from a mean of 25.3 kg (s.d.=12.6 kg) at baseline to 31.4 kg (s.d.=17.8); an increase of 6.1 kg (23.6%) in DMPA users. The ratio of central to peripheral fat mass in DMPA users changed from 0.95 (s.d.=0.155) at baseline to 1.01(s.d.=0.198) at 30 months. In contrast, weight, fat mass and the ratio of central to peripheral fat mass of control participants remained virtually unchanged over the same time period. Women with higher baseline physical activity levels had a smaller increase in body fat (P=0.003) and the fat ratio (P=0.03), but not weight (P=0.48). No other user characteristics including, smoking, past oral contraceptive use or previous pregnancies predicted change in level of fatness. CONCLUSIONS: This study has demonstrated a change in body composition toward greater fatness and toward a central redistribution of fat among DMPA users as compared to controls and provides important information to be used when counseling women regarding contraceptive methods. Given the potential long-term implication of these changes, further study is recommended to determine whether the gains in fatness are reversed following DMPA discontinuation and to examine the role of progestins in the development and maintenance of obesity.

Association between female infertility and agricultural work history.

Lifetime industrial and occupational histories of women with a medically-confirmed diagnosis of infertility (n = 281) were compared to a group of postpartum women (n = 216) for risks of infertility. Controlling for age of first pregnancy or self-report of infertility, date of outcome, cigarette use, and employment in other types of industries, women were at increased risk of infertility if they had worked in industries associated with agriculture (OR = 7.0, 95% CI 2.3-20.8; cases = 11.7%, controls = 1.9%). Among the occupations in which women worked prior to outcome, only those in agriculture were at significantly elevated risk (adj. OR = 11.3, CI 2.6-48.8; cases = 10.0%, controls = 0.9%). Among those who resided on a farm, the risk of infertility was significantly increased (adj. OR = 1.8, CI 1.2-2.7; cases = 37.4%, controls = 25.8%) although yearly duration of farm residence was not (adj. OR = 0.99, CI 0.95-1.03). Farm residence did not alter the OR seen in agricultural industries or occupations. The risk of being diagnosed with an ovulatory or tubal factor increased 4-16-fold among those who had worked in agricultural industries or occupations. These data suggest that, as has been established in men, agriculturally-related exposures may be a significant risk for infertility in women.

A prospective study of bone mineral content and fracture in communities with differential fluoride exposure.

In 1983/1984, a study of bone mass and fractures was begun in 827 women aged 20-80 years in three rural Iowa communities selected for the fluoride and calcium content of their community water supplies. The control community's water had a calcium content of 67 mg/liter and a fluoride content of 1 mg/liter. The higher-calcium community had water with a calcium content of 375 mg/liter and a fluoride content of 1 mg/liter. The higher-fluoride community's water had 15 mg/liter of calcium and 4 mg/liter of fluoride naturally occurring. In 1988/1989, a follow-up study characterized the 684 women still living and available for study. Residence in the higher-fluoride community was associated with a significantly lower radial bone mass in premenopausal and postmenopausal women, an increased rate of radial bone mass loss in premenopausal women, and significantly more fractures among postmenopausal women. There was no difference in the 5-year relative risk of any fracture in the higher-calcium community versus the control community; however, the relative risk was 2.1 (95% confidence interval (CI) 1.0-4.4) in women in the higher-fluoride community compared with women in the control community. There was no difference in the 5-year risk of wrist, spine, or hip fracture in the higher-calcium community versus the control community; however, the 5-year relative risk for women in the higher-fluoride community, compared with women in the control community, was 2.2 (95% CI 1.1-4.7). Estimates of risk were adjusted for age and body size.

Body size, estrogen use and thiazide diuretic use affect 5-year radial bone loss in postmenopausal women.

Understanding factors associated with more rapid bone mineral loss among aging women is important for establishing preventive strategies for intervention. This study reports factors associated with the 5-year change in radial bone mineral density (BMD) determined prospectively in 435 women aged 55-80 years at baseline. The baseline study included measurement of radial BMD (gm/cm2) by single photon densitometry and personal interview. The baseline protocol was replicated 5 years later in a follow-up study. Women with a lower baseline weight or Quetelet index, smaller triceps skinfold and less arm muscle area had significantly greater 5-year bone loss (p = 0.001). Current users of estrogens had less radial bone loss (2.8% vs 7.3%, p = 0.0005) than women not currently using estrogens. Current users of estrogen had significantly less 5-year loss if use had been for 5 years or longer (-1.0% vs -6.9%, p = 0.05). Current users of the thiazide class of medications had less 5-year radial bone loss (5.0% vs 7.4%, p = 0.0035) than women without current thiazide use. Baseline dietary calcium, alcohol consumption and smoking were not associated with BMD change. This suggests that greater body size, and current use of estrogens or thiazide antihypertensives are associated with less radial bone mass loss in a 5-year period among postmenopausal women.