A New Endometriosis Treatment : Nasal Spray May Help Avoid Surgery, Allow Childbirth
The long, frustrating search for a drug treatment to substitute for surgery in most cases of endometriosis--a disease that may affect as many as 15% of all pre-menopausal American women--may be nearing a decisive end, doctors at UCLA and in San Francisco agree.
A cure that can be widely prescribed is not yet at hand, but researchers are optimistic that, if large-scale human trials continue to show promise, a simple nasal spray that can arrest symptoms of endometriosis may be on the market within three or four years.
If the drug therapy lives up to its early promise, six or seven of every eight women with endometriosis may be able to avoid surgery and a large proportion of patients whose fertility has been compromised may find they can give birth.
Potentially, the treatment could eliminate the need for thousands of operations a year for endometriosis, which in the last five years has emerged as one of the most widely publicized of all contemporary women’s health problems. It could also help assure the fertility of many women who now find they cannot have children because of the effects of endometriosis on their reproductive systems.
5 Million May Be Affected
There are no reliable estimates of the total numbers of such surgeries, but the Endometriosis Assn., a Milwaukee-based private group, has estimated there may be as many as 5 million women with the disease. The figure represents, according to the U.S. Food and Drug Administration, an astonishing increase over the 20 cases reported nationally in 1921.
Endometriosis is not a deadly disease, but it has emerged as a key women’s health issue because it affects so many women with the major symptoms of abdominal pain, excessive vaginal bleeding and development of benign, cyst-like growths.
These endometriosis tumors--some as big as grapefruit or even volleyballs--can cluster around and on the ovaries, eventually necessitating a hysterectomy if their development cannot be retarded. Even without hysterectomy, fertility is often reduced or curtailed.
In many cases, even if hysterectomy can be avoided, surgery is necessary to remove endometriosis cysts. Various non-surgical treatments available until now, including a widely used drug called danazol, have all carried with them a frequently unacceptable array of side effects, ranging from development of facial and excess body hair to hot flashes, voice deepening and reduced breast size.
Danazol has also not been as effective in tempering the effects of the disease or forestalling surgery as many doctors would have liked.
Until about five years ago, endometriosis was thought to be a disease of career women--induced, so it was believed, by stress and sedentary life styles. Recently, this stereotype has crumbled and experts have identified it as a disease that affects a wide variety of women--with a clear relationship to the tendency to postpone childbearing into the 30s and 40s.
One drug company, Syntex Laboratories of Palo Alto, is nearing the end of the first of two major procedures mandated by the FDA for approval of the experimental drug in nasal spray form. Researchers working for and with Syntex expect to report, at a national meeting of the Endocrine Society in Anaheim next month, favorable results in more than 100 patients.
At UCLA, researchers working independently are equally optimistic, with several papers already published in prominent journals and more results said to be upcoming. The UCLA team cautions that two side effects must be overcome--though both are thought to be manageable problems.
Both the UCLA and Bay Area research teams are working with the same chemical, called GnRH (for gonadotropin-releasing hormone).
At UCLA, GnRH as a treatment for endometriosis has come under scrutiny by a team headed by Dr. Howard Judd, a professor of obstetrics and gynecology and one of the nation’s foremost experts on endometriosis. The team includes three other top UCLA doctors and internationally known researchers, Wylie Vale and Jean Rivier of the Salk Institute in La Jolla.
Result of Pioneer Work
Judd said GnRH was developed as one result of pioneer work in the early 1970s in the hormone chemistry of the pituitary gland and the hypothalamus--a portion of the brain vital to hormone production--that first isolated the natural form of leutenizing hormone, a similar chemical, from brain fluids of slaughtered animals.
Eventually, researchers learned how to make a synthetic agonist --or a substance that mimics the function of the original chemical--of natural GnRH. By a quirk of chemistry, some experts also believe an antagonist , or a substance that counteracts the original, may also prove effective as a future endometriosis treatment.
Under normal conditions, the pituitary produces small bursts of GnRH every three hours or so, permitting natural regulation of the sequence of functions in the female reproductive system. But in a woman who also has developed endometriosis, symptoms including pain and excess bleeding can develop and cysts can begin to grow if the natural hormone levels are maintained without interruption.
That reality leaves two basic alternatives, Judd said: Interfere with the hormone chemistry so the disease progression stops or surgically remove either the cysts alone or the woman’s entire reproductive system. Obviously, he said, medical interference is preferable.
The trick has been to develop a drug that is capable of turning off the hormone reactions of the ovaries but leaving other hormone chemistry intact and fertility capable of being restarted when endometriosis effects have been sufficiently reduced.
Until now, however, every type of drug therapy used for endometriosis has had unacceptable side effects. Though it remains in widespread use, danazol (marketed under the brand name Danocrine) has been both inconsistently effective in controlling the spread of endometriosis and the source of unsettlingly common side effects.
Far More Control
But when Judd and other researchers started testing GnRH about six years ago, they found that regular doses--which for the moment are administered by nasal spray since GnRH is not effective in pill form--is capable of far more reliable control of the disease than danazol and yields fewer side effects.
Judd and the UCLA team first reported tentative results with five women in 1982. Since then, the UCLA group has had similar successes with several dozen more women.
Of the first 18 patients treated by the UCLA team, only one woman required surgery after GnRH therapy.
“It is clear that we can do what we hoped to do,” Judd said. “It adds another form of therapy for women who suffer from this problem.”
Questions remain, however, posed by the fact that GnRH triggers what is in many ways an artificial, temporary menopause in order to have its beneficial effects. Judd said many women treated with GnRH experience two common symptoms of menopause--hot flashes (just as with danazol) and loss of bone density. The side effects disappeared after therapy was discontinued. Judd said hot flashes can be tempered by adjusting the dose of GnRH or perhaps adding other hormone chemicals to the treatment.
The bone loss problem, he said in an interview, however, “is the big concern that currently exists.”
It isn’t yet clear, Judd and other experts agreed, whether the bone loss is permanent. Most researchers agree bone density will eventually return to normal after the therapy is completed, but Judd and others emphasized that the question must be resolved before GnRH is permitted on the commercial drug market.
