Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone “add-back” therapy

GnRH agonists and add‐back therapy: is there a perfect combination?

“…Regarding add‐back therapy using progestogens alone, androgenic norethisterone starting at a dose of 0.35 mg/day does not alter lipid levels 23 , deleterious effects have been observed with doses of 1.2 mg 40 and 10 mg/day, causing a significant reduction in HDL with no change in LDL 47,50–52 . MPA at 20 mg/day has no effect on HDL or cholesterol levels 49 , when combined with transdermal 17 beta oestradiol 5–10 mg/day alrlo do not modify lipid levels 21,48 .…”

“…Most studies describe a significant loss of bone mineral density at the lumbar spine of 1.5–11.8% after 6 months of GnRH‐a treatment, regardless of the technique used 39,40,47,48,52,65,68,71–85 , although quanititative computed tomography tends to report the higher values. Less uniform data are available for the appendicular skeleton.…”

“…Bone formation and resorption are influenced by 10 mg/day of norethisterone, protecting against bone mineral loss in postmenopausal women 98 or when combined with GnRH‐a 47,50,52,99 . Lower doses (1.2 mg 40 , 1.41 mg 3 , 2.45 mg 80 ) do not eliminate bone demineralisation, and 5 mg fails to demonstrate a significant alteration in urinary markers for bone resorption 100 .…”

“…Sodium etidronate, a biophosphonate, inhibits osteoclast activity, decreasing the incidence of osteoporotic fractures in postmenopausal women with minimal side effects 106,107 . When combined with calcium carbonate and a low dose of norethisterone in a cyclical fashion in women treated with GnRH‐ a, no bone mineral density loss was observed at the lumbar spine 51,52 . However sodium etidronate asa single agent is unlikely to ameliorate vasomotor symptoms and make long term GnRH‐a therapy attractive.…”

“…MPA at doses between 15–100 mg/day also have beneficial effects on hot flushes and sweating 24,26,115 . Tibolone 27,116 (2.5 mg) and norethisterone ranging from 1.41–10 mg 23,47,50,52,99 daily are also effective.…”