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CLINICAL INSIGHTS

Highlights from The 2003 Endocrine Society Meeting

Flashing in perimenopause linked to LH and FSH

Women with high serum levels of LH and FSH are more likely to have hot flashes in anovulatory cycles during perimenopause, according to a substudy of the Study of Women's Health Across the Nation (SWAN). Elevated estrogen or progesterone levels, on the other hand, were not linked to flashes in these women. Presented at the 85th Annual Endocrine Society Meeting in Philadelphia, Pa., this large, multiethnic observational study from Albert Einstein College of Medicine, Bronx, N.Y., also showed a link between progesterone and vasomotor symptoms—but only in ovulatory cycles.

The Daily Hormone Substudy (DHS) of SWAN involved 840 women aged 42 to 52 at baseline, who collected daily, first-morning voided urine samples once a year from menses to menses or up to 50 days and kept daily calendars of vasomotor symptoms. Researchers analyzed the urine samples for LH, FSH, and urinary metabolites of estradiol and progesterone (E1c and Pdg) and looked at the association of vasomotor symptoms across the cycle with integrated daily hormone concentrations, stratified by evidence of luteal activity. Adjustments were made by age, menopause status, body mass index, ethnicity, smoking, and geographic region.

At study end, with 740 cycles available for evaluation, investigators concluded that vasomotor symptoms were more frequent in cycles with no luteal activity than with luteal activity (P=0.0045). Mean integrated Pdg also was higher in symptomatic cycles with luteal activity, compared to symptomatic cycles without luteal activity (P=0.0443), but no other hormones were related to vasomotor symptoms in cycling women. This means that if a woman were symptomatic, she is worse off if she had a larger luteal rise in progesterone metabolites, perhaps because she is "falling from a higher place." Mean integrated LH and FHS were positively associated with vasomotor symptoms in anovulatory cycles (P=0.005 and P<0.0001, respectively).

Santoro NF, the SWAN Daily Hormone Study Writing Group Ob/Gyn & Women's Health. Poster presented at: Endo 2003. The Endocrine Society's 85th Annual Meeting; Friday, June 20, 2003; Philadelphia, Pa. Poster P2-205.

Comment from Nanette F. Santoro, MD, Albert Einstein College of Medicine, Bronx, N.Y.:

The SWAN study links vasomotor symptoms to hormones, strongly suggesting that in the early part of the menopause transition, the likelihood of ovulation drops precipitously, and some symptoms arise as a consequence. What we are seeing in SWAN are "early" transition hot flashes, even when estrogen levels appear relatively stable. In interpreting these results, it is important to remember that urinary estrogens measure substances other than estradiol, and this 'normal' urinary estrogen level could fail to reflect low circulating estradiol.

These hot flashes seem to occur more in women who have cycles that look anovulatory. Later on in the transition, hot flashes are expected to be more common events that are more related to low estrogen, but SWAN offers an explanation for increased symptoms that women report when they are just beginning to experience cycle irregularity.

Metformin reduces hirsutism, acne in PCOS

The first investigation of its kind to specifically address metformin's effects on cosmetic problems has found that the drug significantly improves acne and hirsutism in women with polycystic ovary syndrome (PCOS). The results of the small study were reported by Turkish investigators at The Endocrine Society's Annual Meeting.

The 12-month study enrolled 20 women with PCOS who had hirsutism and acne, as assessed by the Ferriman and Gallwey (F-G) score and patient self-assessment, and lesion counts, respectively. Treatment consisted of 850 mg of metformin twice daily and response was gauged at baseline and after 4, 8, and 12 months.

At the end of the study period, there was a significant improvement in hirsutism scores (F-G score 19.9 vs. 16.3; P<0.01) and patient self-assessment (5.4 vs. 3.8; P<0.01). Inflammatory lesions were reduced by 50.6%, noninflammatory lesions by 40.6%, and acne severity was reduced by 42.4%. Improvements in hirsutism and acne were significantly correlated with improvements in insulin sensitivity. Treatment-related adverse events, most of which were mild, were experienced by 4.3% of the women.

Dereli D, et al. The effect of metformin on hirsutism and acne in polycystic ovary syndrome. Poster presented at: Endo 2003. The Endocrine Society's 85th Annual Meeting; Friday, June 20, 2003; Philadelphia, Pa. Poster P2-176.

ERT improves cognitive processing

While estrogen replacement therapy (ERT) is not of global benefit for cognition in postmenopausal women, it does reduce perseverative errors, according to results of a study presented at The Endocrine Society's Annual Meeting. (Perseverative errors occur when a person uncontrollably repeats his or her response to a previously asked question.) Improvement in vasomotor symptoms did not explain the benefit in this study's population—symptomatic women— suggesting that ERT enhances the efficiency of verbal information processing.

In a double-blind trial, researchers from several centers in Massachusetts randomly assigned 52 women aged 45 to 60 (mean 51.1 years) to transdermal estradiol 0.05 mg/day (n=26) or a placebo patch (n=26) for 12 weeks. Twenty-nine of the women were perimenopausal, 21 were postmenopausal, and two had had hysterectomies but had intact ovaries. Seventeen women had moderate or severe vasomotor symptoms, 16 had mild symptoms, and 19 were asymptomatic.

Before treatment, all of the participants completed a battery of short-term verbal and visual memory and learning skills tests using the California Verbal Learning Test (CVLT). At the end of the trial, the same tests were repeated to determine changes in performance. ERT had no effect on verbal recall (59.2 baseline to 59.8 at study end for treatment vs. 58.0 to 60.6 for placebo). However, it did reduce perseverative errors on CVLT trials one to five more times than placebo (6.5 baseline to 3.7 at study end for ERT vs. 6.2 to 5.6 for placebo; P=0.03). ERT had no effect on tests of other cognitive domains examining attention, verbal, or visual memory. Improvement in verbal recall was significantly correlated with reduction in vasomotor symptoms (r=0.34; P=0.02) but not with improvement in sleep (r<0.01; P=0.95).

Joffe H, et al. Estrogen replacement reduces errors in verbal perseveration, but does not enhance other cognitive domains in menopausal women: a randomized, double-blind, placebo-controlled study. Poster presented at: Endo 2003. The Endocrine Society's 85th Annual Meeting; Friday, June 20, 2003; Philadelphia, Pa. Poster P2-214.

Mammography screening reduces breast cancer mortality

Mammography screening reduces the number of women who die of breast cancer, at least in Sweden and the Netherlands, according to two recently published reviews.

The first study involved 210,000 women aged 20 to 69 years in two Swedish counties. Researchers compared deaths from breast cancer diagnosed in the 20 years before screening was introduced (1958–1977) with those from breast cancer diagnosed in the 20 years following the introduction of screening (1978–1997).

While no significant difference was noted for women aged 20 to 39 years, the researchers calculated a 44% reduction in breast cancer mortality in the second screening period for women aged 40 to 69. Considering reductions in all groups regardless of age and screening status, they calculated an overall 18% reduction in breast cancer mortality over a 20-year period as a result of mammographic screening.

Smaller in size, the second study from the Netherlands reviewed data for 27,948 women between age 55 and 74 who died of breast cancer between 1980 and 1999. Like the previous study, researchers noted a significant decline in breast cancer mortality in 1997 and moving forward in 500 municipalities across the country, reaching a 20% reduction in 2001. They calculated a 1.7% reduction per year for women aged 55 to 74 and a 1.2% reduction per year for women aged 45 to 54.

Tabar L, Yen MF, Vitak B, et al. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet. 2003;361:1405-1410.

Otto SJ, Fracheboud J, Looman CW, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systemic review. Lancet. 2003;361:1411-1417.

It's never too late for a woman to start exercising

Compared with continually sedentary women, women aged 65 years or older who continue to be active or who begin engaging regularly in physical activities such as walking, dancing, gardening, or swimming, have lower mortality rates from all causes, cardiovascular disease (CVD), and cancer, according to recent data from the Study of Osteoporotic Fractures Group. In fact, older women who begin walking just a mile a day can cut their risk of death in half. That the number of older white women in the United States is expected to double in the next 30 years makes the findings particularly important.

The prospective cohort study involved 9,518 community-dwelling white women aged 65 or older. Researchers assessed the women at baseline (between the years 1986 and 1988) and reassessed 7,553 of them approximately 6 years later.

In comparing women who were sedentary at both visits with sedentary women who increased physical activity during the study period, the researchers found significantly reduced death rates from all causes (hazard rate ratio [HRR] 0.52; 95% confidence interval [CI], 0.40–0.69), CVD (HRR 0.64; 95% CI, 0.42–0.97), and cancer (HRR 0.49; 95% CI, 0.29–0.84) independent of age, smoking, body mass index, co-morbid conditions, and baseline physical activity level. Those who were physically active at both visits also had lower rates of mortality from all causes (HRR 0.68; 95% CI, 0.56–0.82) and CVD (HRR 0.62; 95% CI, 0.44–0.88) than sedentary women.

While all of the women benefited from activity, smaller reductions in mortality were noted in women at least 75 years of age and those in poor health. Death resulting from CVD was lowest in women with the greatest increases in physical activity. The risk of dying among active women who became sedentary was similar to that of women who were sedentary all along, indicating that recent physical activity level is a more important predictor of longevity than past levels.

Gregg EW, Cauley JA, Stone K, et al. Relationship of changes in physical activity and mortality among older women. JAMA. 2003;289:2379-2386.

Hormone-releasing IUD reduces bleeding, improves anemia in women with fibroids

Use of a levonorgestrel-releasing intrauterine system (LNG-IUS) dramatically reduces menstrual blood loss in women with uterine leiomyomas, according to a prospective before-and-after study from St. Petersburg, Russia.

The study involved 67 women with at least one uterine leiomyoma of more than 2.5 cm in diameter or multiple leiomyomas of which at least one was 1.5 cm in diameter who use the LNG-IUS as their method of contraception. Researchers measured menstrual blood loss using a pictorial blood loss assessment chart, ferritin and hemoglobin concentrations, and uterine and leiomyoma volume before the onset of treatment and at 3-, 6-, and 12-month intervals.

After 3 months of use, the number of patients diagnosed with excessive menstrual bleeding fell dramatically from 26 to 4. At 12 months, the average patient experienced a sixfold reduction in menstrual blood loss. Other benefits included increased blood hemoglobin and serum ferritin levels.

Uterine leiomyomas account for about half of the 600,000 hysterectomies performed each year in the United States.

Grigorieva V, Chen-Mok M, Tarasova M, et al. Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas. Fertil Steril. 2003;79:1194-1198.

PROFESSIONAL UPDATE

Tort reform bill dies in Senate

H.R. 5, which ob/gyns had hoped would provide relief from skyrocketing liability insurance costs, was defeated in the Senate by a 49–48 vote, 11 short of the 60 needed to overcome Democratic objections to the bill. The Help Efficient, Accessible, Low-Cost Timely Health Care (HEALTH) Act, which would have capped noneconomic malpractice damages at $250,000, was perceived by Democrats as a special-interest measure that "forgets the families and children and elderly people across America who are the victims" of medical errors, according to Sen. Dick Durbin, (D-Ill.).

Some political analysts said the bill had a poor chance of passage for two reasons: It was opposed by a powerful lobby, the Association of Trial Lawyers of America; and Republicans brought the bill to the floor without committee hearings or debate, which often yields the bipartisan compromises needed to pass controversial measures.

According to Charles J. Lockwood, MD, Yale University School of Medicine, "Ob/gyns must take action over the next 18 months to defeat those who have carried out this selfish, callous, and destructive action."

The number of physician extenders is up—and so is their price

Graduating mid-level providers—such as nurse practitioners and physician assistants—are entering the marketplace in droves, according to American Medical News (5/5/03). And, as supply keeps up with demand, employment and salaries are going up.

Statistics from the American Academy of Nurse Practitioners and the American Academy of Physician Assistants show that near-record numbers are graduating from their respective programs. About 5,400 NPs graduated in 2002, with at least that amount expected to graduate this year. Similarly, about 4,300 PAs graduated in 2002, with an expected 4,600 graduates in 2003.

With high demand for these mid-level providers, employment doesn't seem to be a problem for these graduates. Assisted recruitment of NPs and PAs by recruitment firms is down and, according to AAPA's 2002 annual census report, less than 2% of respondents reported being unemployed or looking for work.

Because of the demand, average salaries are increasing. The recruitment firm, Allied Consulting Inc., for instance, found that as a group, recruited NPs and PAs saw their asking price increase by 3.9% from $63,500 in 2001 to $66,000 in 2002.

Despite the high salaries and the increased liability for physicians, mid-level providers can be beneficial to an office practice. They often generate revenue comparable to physicians and can receive Medicare reimbursement.

Program ties bonuses to physician performance

In an effort to encourage physicians to improve their delivery of care, a coalition of physicians, health plans, large employers, and others launched a program that would tie incentive payments to physician performance. The program, Bridges to Excellence, boasts that rewards could equal a 10% raise for qualifying physicians.

The program has three initiatives: Diabetes Care Link to improve diabetes care, Physician Office Link to improve patient care management systems, and Cardiac Care Link to improve cardiac care. The first two initiatives are under way, while the last component is scheduled to be launched later this year.

In Diabetes Care Link—a program modeled after an existing American Diabetes Association/ National Committee for Quality Assurance effort—qualifying physicians who demonstrate good control over their patients' diabetes will receive an annual $100 bonus for each diabetic patient covered by a participating employer or plan.

In Physician Office Link, office practices that implement specific processes to reduce errors and increase quality can qualify for bonuses of up to $55 per year for each patient covered by a participating employer or plan.

Bridges to Excellence, which has the support of the Centers for Medicare & Medicaid Services, is being introduced in Boston, Cincinnati, and Louisville, Ky.—areas that are heavily populated by employees of companies that support the program. Among the participating companies and plans are Cincinnati Children's Hospital Medical Center, Ford Motor Co., General Electric Co., Humana, Procter and Gamble, UPS, and Aetna.

Aetna and physicians settle national class action lawsuit

Aetna and representatives of about 700,000 physicians nationwide have come to an agreement to settle a long-running class action lawsuit over billing and medical decisions. If approved by a federal judge, the $170 million settlement agreement would not only provide some monetary compensation to physicians, but also usher in a new era of cooperation between physicians and managed care companies, the parties involved say.

According to the terms of the proposed agreement, Aetna has agreed to pay $100 million to physicians (equivalent to less than $150 each) and up to $50 million in legal fees. Aetna also agreed to provide $20 million to fund a foundation that would support health-care initiatives such as eliminating racial and ethnic disparities in health care; physicians would have the option of directing their shares of the $100 million settlement to the foundation.

More significant to the physicians involved in the lawsuit are terms in the agreement that outline improvements to the health insurer's physician-related business practices. Among other things, Aetna says it will adopt a clear definition of "medical necessity," reduce administrative complexity in the claims payment system, create a mechanism by which physicians could appeal payment decisions, and establish a National Advisory Committee of practicing physicians to advise the insurer on physicians' concerns.

The settlement agreement received the preliminary approval by Federal District Judge Federico Moreno in May. Final approval or rejection of the settlement is scheduled for October 14. Aetna is the first of nine defendant insurers to settle the lawsuit with physicians.

Florida high court says HMOs liable for network doctors' actions

A health maintenance organization can be held accountable for the actions of a doctor within its network. So ruled the Florida Supreme Court in Rolando Villazon, etc. v Prudential Health Care Plan Inc. The recent decision overturns a lower court's decision that held that the Employee Retirement Income Security Act preempted the lawsuit.

According to American Medical News (5/5/03), federal courts have been moving away from the previously held view that "ERISA preempts just about any claim brought against plans under state law." The high court's ruling puts Florida in line with similar rulings by the US Supreme Court and other state courts.

In Rolando Villazon, etc. v Prudential Health Care Plan Inc., Villazon alleged that a physician under contract with Prudential misdiagnosed or mistreated his wife's tongue cancer—ultimately leading to her death. Although Villazon hadn't claimed that his wife failed to get proper testing or referrals to specialists, the lower court ruled that ERISA preempted the claim because the doctor was an independent contractor and Prudential didn't control the quality of care.

The Florida Supreme Court disagreed. "The Florida Supreme Court said that if an HMO hires a doctor as an independent contractor but still controls aspects of the doctor's practice, such as what is medically necessary or how the doctor must keep records, then the plan can be held responsible," reported AMNews.

The case has been sent back to trial court to determine if the plan is liable.

 

Clinical Insights/Professional Update. Contemporary Ob/Gyn Aug. 1, 2003;48:15-30.