They just won’t stop! We could have predicted this without a study and this was shown with Lupron years ago. It was abandoned because practitioners learned that the health ramifications of low estrogen were detrimental to health and that the reality that patients didn’t do as well as reported. Also, when lupron was stopped the bleeding rapidly returns.
Two issues need to be pointed out here. First, this is a high dose 300mg twice daily Elagolix, higher than the high dose therapy available now (200mg twice daily). The current high dose regimen, 200mg has been shown in their own data to push estrogen levels to a mean of 12 pg/ml, a number rivaling menopause. A higher dose will only further suppress. The so-called add back is 1mg of estradiol orally once per day. In our experience with this dose, we would expect levels of estrogen from 20-70pg/ml. the natural cycle ranges from 30-70 on CD-3, the lowest point to ~ 300pg/ml at ovulation with a mean daily level of 120-200 over the cycle.
Therefore, addback is very minimal in terms of estrogen levels and this over time will result in estrogen deficiency problems, especially for those in the 20 range on addback. This is best expressed by their own admission in the study, “Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.” Attenuated in this context means without addback there would be loss of bone and with addback there is LESS loss of bone, but a loss just the same. With Lupron, use was limited to six months and it was shown that most patients re-couped most of their bone loss but not everyone.
This brings me to the second issue. Mark my words the push from the drug company here is to sell this drug as a long term use drug not the 6-month limitations that were present for Lupron. Give a patient this regimen for 2-3 years and you will have person riddled with problems to include but not limited to: bone loss, migraine headaches, anxiety, depression, weight gain, sleep disturbance, memory loss, attention deficit, hair loss, decreased libido, getting up at night to urinate, frequency and urgency of urination, vaginal dryness, night sweats, and hot flashes.
This is by no means an exhaustive list. As always, history repeats itself. We lived with Lupron for about 15 years before most practitioners wised up to its reality.
Michael D. Fox, MD
Jacksonville Center Reproductive Medicine
Advanced Reproductive Specialists
https://www.nejm.org/doi/full/10.1056/NEJMoa1904351