Research eyes expanded use for intrauterine systems in women

New uses examined for women's health at international symposium

(Editor's note: This article discusses off-label use of the levonorgestrel intrauterine system.)

Consider the many treatment options when presented with the following cases: the perimenopausal woman with prolonged menstrual bleeding due to uterine leiomyomas; the young woman with significant pain from spreading endometriosis; and the mother with menorrhagia. Which options will you choose?

Medicated intrauterine systems (IUS) may represent a treatment choice in each of these conditions, according to new research presented in October 2006 at the Fifth International Symposium on Intrauterine Devices and Systems for Women's Health. Findings presented at the symposium, sponsored by the Population Council in cooperation with the United Nations Population Fund, highlight the number of uses for such intrauterine devices (IUDs) outside contraception, says Elof Johansson, MD, PhD, president of the Population Council's Center for Biomedical Research.

While the copper IUD (marketed in the United States as the ParaGard IUD, Duramed, a subsidiary of Barr Pharmaceuticals) is the most-used reversible contraceptive in the world, its use in the United States and part of Europe may be low due to misconception of risks, he reports. This fear is unfounded, says Johansson, as research shows there is no increased risk of infections during use.1

The levonorgestrel IUS (marketed in the United States as Mirena LNG IUS, Berlex) works by changing the milieu in the cavity of the uterus, explains Johansson. It also inhibits growth of the endometrium, which makes menstrual bleedings small or absent while the cyclic estrogen production in the ovary is intact, he notes.

Use of the LNG IUS is increasing fast in the United States — now more than 1 million users — and there are strong increases in Europe and upward growth in developing countries, Johansson reports. Since anemia is common in developing countries, use of the device would aid in combating the problem, because research has shown the device reduces menstrual blood loss, which results in improvement of the body iron balance and in an increase in hemoglobin concentration.2

IUS for fibroids?

The progestin-releasing IUS provides effective contraception, reduces menstrual bleeding, and likely reduces menstrual pain in women with uterine fibroids, says Andrew Kaunitz, MD, professor and assistant chair in the Obstetrics and Gynecology Department at the University of Florida Health Science Center/Jacksonville. Kaunitz presented on progestin-releasing intrauterine systems and leiomyoma at the recent Population Council symposium.

Uterine leiomyomas are the most common benign pelvic tumors found in women. Prevalence data varies. Some studies indicate as many as 70% premenopausal women have fibroids.3

In a 2003 study, researchers reported a dramatic reduction in menstrual blood loss accompanied by an improvement in hematological indices in patients with uterine leiomyomas who were treated with the LNG IUS for one year.4 In a study of menorrhagic patients with submucous leiomyomas, researchers found the LNG IUS was as effective as thermal balloon ablation in treating excessive bleeding and related anemia.5

There are caveats to device use for uterine fibroids, notes Kaunitz. Long-term symptomatic relief is not guaranteed, and in the case of the levonorgestrel IUS, it is not likely to effectively treat such nonmenstrual fibroid symptoms as pressure. Expulsion rates appear acceptable, but are higher than in women without fibroids, he notes. However, for selected women with symptomatic fibroids seeking treatment, the LNG-IUS represents an appropriate option prior to proceeding with surgery, says Kaunitz.

Use of the LNG IUS may offer an effective approach in treating endometriosis, according to research presented at the recent symposium.6 Endometriosis is defined as the presence of endometrial tissue in abnormal locations such as the ovaries, fallopian tubes, and abdominal cavity. It is estimated that endometriosis affects almost 10% of women of reproductive age; 70%-90% of women with chronic pelvic pain, dysmenorrhea, dyspareunia, infertility or menstrual disturbances have endometriosis.7

To evaluate the effectiveness of the LNG IUS in treating endometriosis-related pain, Brazilian researchers conducted a randomized controlled clinical trial using LNG IUS and a gonadotrophin-releasing hormone (GnRH) analogue, the gold standard drug treatment for endometriosis. Eighty-women were enrolled in the six-month trial.

Both the LNG IUS and the GnRH analogue were effective in the treatment of chronic pelvic pain associated with endometriosis, although no differences were observed between the two treatments. Since the LNG IUS does not provoke hypoestrogenism and only requires one medical intervention for its introduction every five years, the device may represent an effective option for endometriosis treatment, the researchers conclude.8

Look at options

Women moving into the perimenopause may experience menorrhagia or dysfunctional uterine bleeding. When they reach menopause, some women who choose combined hormone therapy may experience bleeding/spotting due to use of continuous progestin for endometrium suppression.9 The LNG-IUS may aid in relieving these problems in peri- and postmenopausal women.9

What are some of the benefits of use on the LNG-IUS in the perimenopause? The device prevents ovulation, which is important for those women who continue to have ovulations prior to menopause, says Régine Sitruk-Ware, MD, executive director of the Population Council's Product Research and Development Division. It also protects the endometrium from overproliferation, states Sitruk-Ware, who presented on use of the device in postmenopausal women at the symposium.10

"In the perimenopause, high secretion of estradiol from the ovaries is still possible and there are very few ovulations, hence very low levels of progesterone to oppose the proliferative effects of estrogen on the endometrium," she notes. "Therefore, the progestin contained in the IUS and delivered directly into the uterine cavity compensates for that lack of progesterone and prevents the excessive stimulation of the tissue by the estrogen."

Women in the perimenopause who experience dysfunction bleeding may look to hysterectomy for relief. A new systematic review of scientific studies indicates that while use of conservative surgery reduces blood loss more than the IUS, the two treatments appear about equal in terms of patient satisfaction.11

References

  1. Shelton JD. Risk of clinical pelvic inflammatory disease attributable to an intrauterine device. Lancet 2001; 357:443.
  2. Luukkainen T. The levonorgestrel intrauterine system: Therapeutic aspects. Steroids 2000; 65:699-702.
  3. Day Baird D, Dunson DB, Hill MC, et al. High cumulative incidence of uterine leiomyoma in black and white women: Ultrasound evidence. Am J Obstet Gynecol 2003; 188:100-107.
  4. Grigorieva VA, Chen-Mok M, Tarasova MA, Mikhailov AV. Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas. Fertil Steril 2003; 79:1,194-1,198.
  5. Soysal S, Soysal ME. The efficacy of levonorgestrel-releasing intrauterine device in selected cases of myoma-related menorrhagia: A prospective controlled trial. Gynecol Obstet Invest 2005; 59:29-35.
  6. Bahamondes L. Endometriosis and dysmenorrhea. Presented at the Fifth International Symposium on Intrauterine Devices and Systems for Women's Health. New York City; October 2006.
  7. Bahamondes L, Petta CL. The levonorgestrel-releasing intrauterine system (Mirena) in endometriosis and dysmenorrhoea. Gynaecology Forum 2006; 11:22-24.
  8. Petta CA, Ferriani RA, Abrao MS, et al. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 2005; 20:1,993-1,998.
  9. Sturdee D. The levonorgestrel-releasing intrauterine system (Mirena) in the peri- and postmenopause. Gynaecology Forum 2006; 11:25-27.
  10. Sitruk-Ware R. LNG IUS in postmenopausal women. Presented at the Fifth International Symposium on Intrauterine Devices and Systems for Women's Health. New York City; October 2006.
  11. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev 2006; 2:CD003855.