Dienogest Versus Leuprolide: Pain Relief and the Bone-Density Subgroup

An endometriosis prescription discussion needs more than a comparison of pain scores. Ask about the exact regimen, bleeding changes, bone health, pregnancy plans and the date you will review whether treatment is helping.

What the pain trial compared

A 2010, 24-week trial¹ randomized 252 women with confirmed endometriosis: 124 to oral dienogest 2 milligrams daily, and 128 to leuprolide acetate 3.75 milligrams by depot intramuscular injection every four weeks. It was an open-label, non-inferiority trial, meaning participants knew their treatment and the study tested whether dienogest was acceptably close to the comparator.¹

Average pelvic-pain scores on a visual analogue scale fell by 47.5 millimeters with dienogest and 46.0 with leuprolide. The investigators concluded that dienogest met the comparison’s efficacy criterion. That finding does not mean every participant became pain-free or that the treatments are identical for every patient.¹

Hot flushes were reported less often with dienogest, while bleeding episodes were suppressed less than with leuprolide.¹

How many women had bone measurements?

The trial reported mean lumbar bone-mineral-density changes of +0.25% with dienogest and −4.04% with leuprolide. These were subgroup measurements, not results from all 252 participants.¹

The current UK product information for Dimetrum, a 2-milligram dienogest tablet, gives the subgroup sizes: 21 adults taking dienogest and 29 taking leuprorelin, another name for leuprolide. It says long-term bone-density and fracture-risk data for dienogest users are not available. It also describes bone-density loss in an adolescent study and calls for careful assessment in people at increased osteoporosis risk.²

A small six-month measurement cannot establish what happens to bone strength or fracture risk over several years.

A later review changes the longer-term discussion

A 2026 systematic review and meta-analysis searched through July 2025 and included 37 studies across several endometriosis treatments. For dienogest, pooled bone-density changes were −0.83% at six months across six studies and −1.91% at 12 months across four. The authors reported high heterogeneity and inconsistency between studies.³

Those pooled results do not mean every person loses that amount of bone density. They also do not provide a direct repeat of the 2010 head-to-head comparison. The review concluded that the clinical significance of the observed changes remains uncertain.³

Bring previous fractures, known low bone density and other bone-risk information to the consultation. Ask whether an assessment or monitoring plan is appropriate for your treatment duration.

Ask which regimen is actually being offered

ESHRE’s 2022 endometriosis guideline recommends considering GnRH agonists as second-line treatment because of their side-effect profile. It advises considering combined hormone add-back alongside a GnRH agonist to help prevent bone loss and low-estrogen symptoms.⁴ Ask whether your proposed leuprolide regimen includes add-back, and how that affects the evidence being used to explain its risks.

For dienogest, check the exact product licensed where you receive care. The UK Dimetrum information states that it is not a contraceptive and advises nonhormonal contraception if needed. It also warns that heavy, continuous bleeding can cause anemia, including severe cases, particularly when conditions such as adenomyosis or fibroids are present.² Agree whom to contact if bleeding changes or pain remains disruptive.

Period, Handled discusses “Bringing It to the Appointment” in Chapter 8, “When Pain Is a Message.” It recommends recording what pain prevented and bringing previous treatments with their duration. Those details help define what improvement would matter to you.