HRT utilization patterns change in aftermath of WHI findings

Drug Cost Management Report, August 29, 2003

It has been over a year since the Women's Health Initiative (WHI) halted clinical trials on hormone replacement therapy (HRT) due to a determination that use of estrogen/progestin for management of menopausal symptoms causes more problems than it solves. Due to the WHI findings, FDA advised women to minimize their use of HRT to the lowest dose and shortest duration they are comfortable with.

This left approximately 6 million women and their physicians to make some difficult choices about discontinuing HRT. It also provided new market opportunities for alternative products to manage menopausal symptoms or to mitigate side effects of HRT for women who choose to continue the therapy.

As of the second quarter of 2003, nine out of 15 PBMs surveyed list Premarin (estrogen) among their top 10 most heavily utilized brands. The Inteq Group, an 800,000-member PBM, lists Premarin as its most heavily utilized product. Some of the largest PBMs, such as WellPoint Pharmacy Management and PharmaCare Management Services, Inc., also report Premarin among their top 10 drugs by utilization. For comparison purposes, the frequency with which Premarin was named as a top-10 product puts it in the same league as Prevacid and Zyrtec in terms of utilization. The only other products named more frequently were Lipitor, Zithromax and Zoloft. No other HRT products were named by the PBMs.

HRT Utilization Declines

Nevertheless, HRT utilization is declining. Express Scripts has seen a dramatic decrease in the use of combination HRT among its members. Of those members on combination therapy, 36% discontinued usage in 2002, after the WHI findings, as compared with 8.4% in 2001. Likewise, the percentage of new combination HRT members in 2002 decreased from 14.1% to 6.7%.

Estrogen-only users discontinued HRT therapy as well. Despite the fact that no detrimental effects of estrogen-only treatment were reported in the WHI, utilization of estrogen therapy decreased by 22.6% from 2001's 9.5% decline. Utilization of alternative agents to treat osteoporosis, such as Evista, Fosamax and Actonel increased by 42.3% in 2002 as compared with 27.7% in 2001.

Blue Shield of California, with more than 2 million covered lives in the pharmacy benefit, has also seen a decline in utilization of HRT. Blue Shield of California examined pharmacy claims data for postmenopausal women for five months before and five months after the study findings were released, and also compared the figures with data for the same five-month periods in the previous year. According to Nancy Stalker, Pharm.D., vice president of pharmacy services, the percentage of HRT users was on the decline prior to the WHI publication, but "the rate of decline essentially tripled following the publication."

As with Express Scripts' members, there were significant declines in the number of Blue Shield of California members on both combination and estrogen-only therapy post WHI. This decline was greater in combination HRT users, however. Likewise, prescriptions for the period before the publication of the WHI findings and post publication have also decreased for HRT drugs. The decrease in utilization has resulted in a shift in utilization patterns among HRT users. Women are using hormone therapy for a shorter duration, to manage the worst of their menopausal symptoms.

Bernard Poussot, president of Wyeth, a market leader for hormone therapy, reported in a first-quarter 2003 earnings conference call that the majority of Premarin and Prempro (estrogen/progesterone) users are under age 65. The mean age of users is on the decline, as fewer women stay on HRT for the long term. According to Poussot, "the average of people using the product long term and new users would be less than two years. This is declining and explains the decrease in prescriptions."

Premarin-Related Sales Slide

The Premarin family of products has taken a hit since the WHI. Wyeth reported that for the fourth quarter of 2002, sales for the Premarin family of products were down 21%. For full-year 2002, sales were down 9%. 2001 was the peak year for these therapies, with $2.1 billion in sales.

Poussot reports that more than 90% of prescriptions are driven by the desire to reduce menopausal symptoms. HRT is still the most effective therapy for symptoms such as hot flashes. Wyeth makes Premarin, Prempro and Premphase, and recently received FDA approval for a lower-dose version of Prempro. Poussot says physicians will readily accept low-dose Prempro because of its FDA support.

Another reason for HRT usage has historically been for prevention of osteoporosis. Prior to the WHI, HRT was the prevailing therapy for prevention of bone loss. The benefits of HRT on bones are connected to how recent HRT usage is, not the duration of use. Therefore, it is important for women discontinuing HRT to find alternative agents for osteoporosis. Alternate drug agents most frequently prescribed for osteoporosis are:

* Fosamax, for which Merck anticipates 2003 sales in excess of $2.6 billion.