Partially suppressing levels of the female sex hormone estradiol could be a new way of managing endometriosis, according to a study.
And a new class of therapy could make partial suppression possible without triggering harmful side effects, researchers said.
The study, “Partial suppression of estradiol: a new strategy in endometriosis management?,” was published in the journal Fertility and Sterility.
Ovulation, menstruation and female hormones known as estrogens are all involved in the development of endometriosis, a condition in which tissue that normally grows inside the uterus grows outside it.
This suggests that hormone therapies that suppress ovulation and menstruation, and reduce estradiol to levels similar to what is seen after menopause, could be a way to treat endometriosis. Estradiol is the primary female sex hormone.
It is important to maintain a certain level of estradiol when a treatment is administered, however, researchers said. Otherwise, a woman can have side effects such as night sweats, hot flashes, vaginal dryness, and loss of bone mineral density.
“Partial suppression of estradiol within the 20-60mg/ml range could be the optimal compromise between efficacy, tolerance and safety,” the authors wrote.
For some time, doctors have achieved partial estradiol suppression with a combination of gonadotrophin releasing hormone (GnRH) agonists, plus estrogen and progestin. GnRH agonists are molecules similar to GnRH, the hormone that stimulates the production of estradiol and another female sex hormone, progesterone.
But this treatment approach has several drawbacks. For example, estrogen can trigger the progression of endometriosis as well as increase the risk of thrombosis and embolism, especially in middle-aged women. Thrombosis is blot clotting. An embolism is a blood-vessel obstruction.
Scientists have recently developed a new class of drugs that can partially suppress estradiol. They act as a GnRH antagonist or suppressor by binding to the GnRH receptor in the brain’s pituitary gland, preventing the receptor from functioning.
Normal GnRH binding prompts the pituitary gland receptor to produce the hormones LH and FSH, which stimulate the ovaries to produce estradiol and progesterone.
By preventing GnRH from binding to the receptor, GnRH antagonist drugs inhibit the ovaries’ production of estradiol and progesterone.
Importantly, the bigger the GnRH antagonist drug dose a patient receives, the less estradiol is produced. That suggests that partial suppression can be achieved with the right dose of the treatment.
All four are in Phase 2 and Phase 3 clinical trials. Initial results indicate they can reduce the pain caused by endometriosis.
“By offering the possibility of personalized dosing … GnRH antagonists could well show potential advantages over other therapies,” the authors said, although they added that studies are needed to compare the drugs’ benefits with those of other endometriosis treatments.
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