Nancy E. Reame

Health-related quality of Life issues in women with polycystic ovary syndrome

OBJECTIVE To evaluate the influence of obesity, fertility status, and androgenism scores on health-related quality of life in women with polycystic ovary syndrome (PCOS). DESIGN Cross-sectional, correlational. SETTING Private reproductive endocrinology practice in two southeast U.S. cities. PARTICIPANTS Convenience sample of 128 women with PCOS, half of whom were attempting to conceive in addition to being treated for PCOS. Most were White (97%), married (78%), with a mean age of 30.4 years (SD +/- 5.5). MAIN OUTCOME MEASURES The Health-Related Quality of Life Questionnaire (PCOSQ) for women with polycystic ovary syndrome. A laboratory panel and clinical measures, including body mass index, waist-to-hip ratio, and degree of hirsutism. RESULTS The most common health-related quality of life concern reported by women with PCOS was weight, followed in descending order by menstrual problems, infertility, emotions, and body hair. CONCLUSIONS The psychological implications of PCOS are easily underestimated and have been largely ignored. Nursing has a pivotal role in recognizing these concerns and implementing therapy to improve quality of life in women with PCOS.

Perimenstrual symptoms among Chinese women in an urban area of China

We explored perimenstrual symptoms among 16 Chinese women in an urban area of southeastern China using a retrospective questionnaire, the Menstrual Distress Questionnaire (MDQ), and a prospective daily symptom diary, the Daily Health Diary (DHD), modified for cultural relevance. Mean scores on the DHD were significantly (p < .03) higher during the perimenstrual phase for the symptoms fatigue, increased sensitivity to cold, increased sleeping, abdominal pain/discomfort, painful or tender breasts, and decreased sexual desire. The women who reported higher DHD physical symptom scores prospectively were more likely to recall more severe physical symptoms retrospectively on the MDQ. However, there were remarkable discrepancies between the DHD and MDQ regarding psychoemotional symptoms. By retrospective MDQ, the percentages of women who experienced severe mood swings and irritability ranged from 13% to 25% during the premenstrual and menstrual phases; on the DHDs, however, these emotional symptoms were not statistically associated with the menstrual cycle. The failure of prospective charting to confirm the retrospective reports of cyclic psychoemotional symptoms agrees with findings of studies of U.S. samples. We conclude that perimenstrual distress in Chinese women may be affected by the data collection methods.

PULSATILE LH SECRETION IN WOMEN WITH PREMENSTRUAL SYNDROME (PMS): EVIDENCE FOR NORMAL NEUROREGULATION OF THE MENSTRUAL CYCLE

The premenstrual syndrome (PMS) has been proposed to result from excessive exposure to and/or withdrawal of brain opioid activity during the luteal phase. Because hypothalamic opioids are believed to modulate GnRH secretion, in part under the influence of ovarian steroids, we performed longitudinal studies of gonadotropin and ovarian steroid secretion across ovulatory, symptomatic cycles of 17 PMS patients and 8 normal volunteers. Pulsatile LH secretion was measured every 10 min for 8 hr at times when central opioid activity was expected to be low (early follicular phase), high (mid-luteal phase; ML), and declining (late luteal phase). In both subject groups, a cycle-phase effect was observed for LH pulse frequency (p = < 0.001) and amplitude (p = 0.002), and for the transverse mean concentrations of LH (p = 0.05), FSH (p < = 0.001), estradiol (E2) (p = < 0.001) and progesterone (P) (p = < 0.001). ML P secretion in PMS patients was pulsatile, and mean concentrations (over 30-60 min) were similar to those of normal controls. The changes in pulsatile LH secretion across the cycle were not different in the PMS patients compared to the normal women, though mean FSH in the ML phase was higher in the PMS group (p = < 0.05). The similar changes in luteal LH pulse frequency fail to provide evidence that GnRH secretion is impaired, thus challenging the view that the neuroregulation of the menstrual cycle in women with PMS is markedly altered.

Differential associations for menopause and age in measures of vitamin K, osteocalcin, and bone density: a cross-sectional exploratory study in healthy volunteers.

Objective: To distinguish the effects of midlife aging from early postmenopause on vitamin K measures, bone formation biomarkers, and bone density. Design: Cycling older volunteers (CO; 40-52 years, n = 19) were compared to cycling young (CY; 20-30 years, n = 21) and untreated, age-matched women in the early postmenopause years (EPM; 40-52 years, mean years PM = 2.8 ± 0.5, n = 19). We assessed sex steroids, vitamin status (phylloquinone, 25-hydroxyvitamin D, retinol), osteocalcin (OC), percentage of undercarboxylated osteocalcin (%ucOC), and bone mineral density (BMD) at the spine and hip with dual-energy x-ray absorptiometry. Results: CO women had similar estradiol and vitamin status as CY women, but lower OC (0.64 ± 0.04 vs 0.97 ± 0.08 nmol/L, P = 0.01) and BMD at the total hip (1.0038 ± 0.032 vs 1.1126 ± 0.030g/cm2, P = 0.02). In the two older groups, BMD was similar at all sites, but OC was elevated in the EPM women (1.10 ± 0.10 vs 0.64 ± 0.04 nmol/L, EPM vs CO, P = 0.001). Although phylloquinone was highest in the EPM women, %ucOC was also higher when compared with all cycling women (21.9 ± 1.7% vs 17.4 ± 0.9%, n = 40; P = 0.02). Conclusions: Premenopausal women show reduced BMD despite normal estrogen profiles. %ucOC may be a specific bone marker of the early postmenopause in healthy women.

Creating a New Structure for Research on Health Care Effectiveness

Effectiveness research (a term we use in preference to the more confining and difficult health services or outcomes research) evaluates the clinical setting and the health care system on which it depends. It uses a variety of health care assessment techniques and the practical clinical trial to inform clinical practice, quality interventions, and health policy decisions. Effectiveness research had not had sufficient public or private funding to produce the information needed to facilitate evidence-based health care improvement. However, recent trends, such as the likelihood for continued substantial increases in health care costs and concern regarding the quality and safety of the US health care system, are among the important arguments for increasing its funding and capacity. We propose a new entity, a public-private consortium to expand and offer new capability and resources in this area. The consortium would consist of all relevant public and private entities. It would be organized into an executive committee, which would identify research priorities and panels to design requests for proposals. Competitive peer-reviewed proposals, transparency and balance of forces in choice of topics, conduct of research, and interpretation of results would be important features. Metrics for success would be use of the data derived from consortium projects in medical decision making and benefit design. The consortium would provide balance and potential mediation of conflicting or competing interests in which all stakeholders will be present to establish the rules. Broad representation of all interests would serve to avoid the economic, policy, and political issues that have bedeviled past efforts. Models for the consortium include the Health Effectiveness Institute, the Centers for Education and Research on Therapeutics, and the Transportation Research Board.

Midlife Women's Responses to a Hospital Sleep Challenge: Aging and Menopause Effects on Sleep Architecture

OBJECTIVE To distinguish aging from menopause effects on sleep architecture, we studied an episode of disturbed hospital sleep in asymptomatic midlife women during the follicular phase of an ovulatory cycle and three control groups differing by age or menopause status. METHODS Fifty-one studies were conducted in four groups of volunteers: young cycling (YC, 20-30 years, n = 14), older cycling (OC, 40-50 years, n = 15), ovariectomized receiving estrogen therapy (OVX, 40-50 years, n = 12), and spontaneously postmenopausal (PM, 40-50 years, n = 10). Subjects were admitted to the University Hospital General Clinical Research Center (GCRC) for a first-night sleep study conducted during a 24-hour, frequent blood sampling protocol. RESULTS Despite similar estrogen concentrations in the YC (28 +/- 4 pg/ml) and OC (34 +/- 6 pg/ml) groups, OC women had reduced sleep efficiency (79% +/- 2%) vs. YC (87% +/- 3%; p = 0.009). In the OVX and PM groups where estrogen concentrations were markedly different, sleep efficiency was also reduced vs. the YC group (OVX vs. YC, 79% +/- 3% vs. 87% +/- 3%, p = 0.05; PM vs. YC, 75% +/- 3% vs. 87% +/- 3%, p = 0.007). Wake time was longer in the three older groups (103 +/- 10 minutes, 101 +/- 12 minutes, 123 +/- 12 minutes for OC, OVX, PM, respectively) vs. YC (63 +/- 13 minutes, p < 0.05). The number of stage shifts was positively associated with advancing age (rho = 0.3, p < 0.03) but not with estrogen concentration. CONCLUSIONS Aging-related sleep deficits in response to an experimental stressor occur in midlife women prior to menopause.

Surrogate pregnancy: Clinical features of forty-four cases

This record analysis describes the obstetric outcomes of a series of 44 pregnancies occurring in 41 women who underwent donor insemination as participants in a private surrogate parenting program between 1981 and 1985. The typical surrogate mother was 25 years old with a high school education and married with one child 2 years old. Twenty-nine percent of the sample reported no source of income other than welfare. Two thirds of the histories included at least one of the following perinatal risk factors: smoking (n = 19), low annual income (n = 15), unmarried status (n = 12), or parity of 0 or greater than 4 (n = 5). Six losses occurred in the first or second trimester. Thirty-nine viable infants were born to 37 women and include one set of fraternal twins. Three of the singleton newborns weighed less than 2500 gm; newborn morbidity after preterm delivery occurred in one case. Women with complications (n = 14) were similar in maternal age, education, parity, annual income, marital status, and smoking history to women without complications (n = 24). A role for psychosocial stress and financial motivation in the etiology of these outcomes is explored.

Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics

OBJECTIVE To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. DESIGN Prospective observational study. SETTING National Center for Infertility Research at Michigan. PATIENT(S) Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women.Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. MAIN OUTCOME MEASURE(S) Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E(2), P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. RESULT(S) Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 +/-.51 vs. 4.03 +/-.33 [mIU/mL +/- SEM]; FSH: 5.81 +/-.63 vs. 3.80 +/-.45) but were not different at any other phase of the cycle. CONCLUSION(S) These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.

Concentrations of Follicle-Stimulating Hormone Correlate with Alkaline Phosphatase and a Marker for Vitamin K Status in the Perimenopause

Serum alkaline phosphatase (ALP), a gross marker of bone turnover, has been reported to be elevated after menopause, a period characterized by hallmark increases in follicle-stimulating hormone (FSH). Whether the ALP rise coincides with the perimenopausal transition when changes in FSH, estrogen levels, and menstrual cycles are first apparent is not known. The purpose of this cross-sectional study was twofold: (1) to characterize the influence of the perimenopausal transition on ALP activity and (2) to correlate ALP activity with more precise markers for bone, osteocalcin (OC), and vitamin K status assessed with undercarboxylated osteocalcin (ucOC). Thirty-eight studies of hourly FSH were conducted on cycle day 6 of the follicular phase in perimenopausal women volunteers, aged 40-54 years (mean body mass index [BMI] = 24.2 +/- 0.5). Mean FSH was used to define the perimenopausal stage (early perimenopausal, mean FSH </= 15 IU/L, n = 27; late perimenopausal, mean FSH > 15 IU/L, n = 11). As expected, late perimenopausal women had irregular and longer menstrual cycles, lower estradiol (E(2)) and estrone (E(1)) levels, and a lower frequency of ovulations vs. the early group. ALP was higher (76.5 +/- 8.3 vs. 58.3 +/- 2.7 IU/L, p = 0.045) compared with the early perimenopausal group. In a subsample (n = 10), OC was associated with ALP (r = 0.69, p < 0.03), FSH was positively related to ucOC concentrations (r = 0.7, p < 0.03), and women with E(1) concentrations <40 pg/ml had double the percentage of ucOC compared with those where E(1) was >40 pg/ml (46.3% +/- 6.6% vs. 22.0% +/- 3. 1%, p < 0.006). Clinical markers of the perimenopause are associated with a nonspecific but inexpensive marker of enhanced bone turnover (i.e., higher ALP) and correlate well with more precise markers of bone activity. These findings suggest that health-promotion strategies for preserving bone should be instituted well before the last menstrual period.

The surrogate mother as a high-risk obstetric patient

A number of medical and public policies are recommended in the revised statement on surrogate motherhood by the Committee on Ethics of the American College of Obstetricians and Gynecologists (ACOG), 1 which expands and replaces the original committee opinion of 1983. Some of the implications with respect to the physician-patient relationship have been laid out in the updated statement, whereas others may only become evident as the practitioner increasingly encounters this population of obstetric patients and the affected families. This commentary examines how the implementation of the revised ethical guidelines may affect and refine future practice.