In my practice I begin therapy at a dosage of 5 mg/d; the drug is effective for most patients at that dosage. If 5 mg/d does not reduce pain, I increase the dosage by 2.5 mg (half of a tablet) daily every 4 weeks, to a maximum dosage of 10 mg/d (two tablets). If that dosage is ineffective, I usually discontinue NEA and switch to a GnRH agonist.
Depot medroxyprogesterone acetate; oral medroxy-progesterone acetate
DMPA is available in two FDA-approved formulations:
- a 150-mg dose given by intramuscular injection every 3 months
- a 104-mg dose given by subcutaneous injection every 3 months.
Research. The results of two large clinical trials, comprising a total of more than 550 subjects, showed that DMPA (104 mg, SC, every 3 months) and depot leuprolide (11.25 mg, IM, every 3 months or 3.75 mg, monthly) were each equally effective in relieving dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and pelvic induration in women who had endometriosis.9,10
DMPA was associated with a greater rate of episodes of irregular bleeding than depot leuprolide; conversely, depot leuprolide was associated with greater loss of bone density and a higher incidence of vasomotor symptoms. Weight gain was in the range of 0.6 kg in both groups.
Of note, DPMA is much less expensive than depot leuprolide.
Another study showed that increasing the dosage of DMPA did not improve efficacy over the standard dosage11: DMPA, 150 mg IM, monthly, and DMPA, 150 mg IM, every 3 months produced similar relief of pelvic pain.
Oral medroxyprogesterone acetate, prescribed at high dosages, is also effective for pelvic pain caused by endometriosis. In a pilot study (n=21), oral MPA, 50 mg/d for 4 months, alleviated dysmenorrhea, dyspareunia, pelvic pain, dyschezia, and pelvic tenderness and decreased pelvic nodularity. Sixty percent of subjects reported weight gain— 1.5 kg, on average.12
Progestin-releasing devices: Mirena and Implanon
Many pilot studies have reported that the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for pelvic pain caused by endometriosis.13-17 For example:
Research. In a small clinical trial, 30 women who had pelvic pain and endometriosis were randomized to receive an LNG-IUS (Mirena) or DMPA, 150 mg IM, every 3 months for 3 years.13 Both therapies were effective at reducing pelvic pain.
At the conclusion of the study, more women opted to retain the LNG-IUS (87%) than to continue DMPA injection (47%). Bone density was maintained in women who had the LNG-IUS placed but slightly diminished in women receiving DMPA.
In a pilot study of an etonogestrel releasing implant (Implanon), 41 women who had pelvic pain and endometriosis were randomized to receive the implant or DMPA, 150 mg IM, every 3 months for 1 year.18 Both therapies were similarly effective at reducing pelvic pain.
Notably, irregular uterine bleeding is a common problem when the etonogestrel-releasing implant is used to treat endometriosis. Achieving amenorrhea or oligomenorrhea is an important goal for women who suffer from pelvic pain caused by endometriosis.
My recommendation
Most ObGyns see patients who are suffering from difficult-to-treat pelvic pain caused by endometriosis. Many of these patients have not had a trial of a progestin, such as NEA, DMPA, or the LNG-IUS that I use in my practice.
Progestins are, as I’ve described, effective for pelvic pain. They are also relatively inexpensive and have a side-effect profile that most patients find acceptable. I recommend that you try a progestin for your patients who have refractory pelvic pain.
What is your preferred hormone treatment for women with unrelieved pelvic pain from endometriosis?