What are the potential side effects of dienogest (progestin) in a woman with adenomyosis?

Dienogest Side Effects in Women with Adenomyosis

Dienogest is generally safe and well-tolerated for adenomyosis treatment, but abnormal uterine bleeding (particularly metrorrhagia) is the most common and clinically significant side effect, occurring in approximately 55% of patients and leading to treatment discontinuation in 22% of cases. 1, 2

Most Common Side Effects

Bleeding-Related (Most Frequent)

• Abnormal uterine bleeding occurs in 55% of patients (95% CI 37-73%), representing the most prevalent adverse effect 1
• Amenorrhea develops in 17% of patients (95% CI 2-42%) 1
• Metrorrhagia severe enough to cause treatment discontinuation occurs in approximately 22% of cases, particularly in women with larger uterine size 2, 3
• Worsening anemia due to metrorrhagia can occur, with five of 17 patients (29%) experiencing this complication in one study 4

Other Common Side Effects

• Swelling/edema occurs in 13% of patients (95% CI 3-28%) 1
• Abdominal pain affects 1% of patients (95% CI 0-3%) 1
• Nausea and vomiting have been reported in both clinical trials and FDA adverse event databases 1
• Back pain is documented in both systematic reviews and FAERS database reports 1

Serious but Uncommon Side Effects

Bone Health

• Decreased lumbar spine bone mineral density (BMD) can occur with long-term use, though dienogest demonstrates modest estradiol suppression (maintaining levels >50 pg/mL) which may mitigate this risk 4, 1

Psychiatric Effects

• Depression has been reported as a serious adverse reaction requiring monitoring 1

Rare Serious Events

• Hemorrhagic shock has been documented in post-marketing surveillance 1
• Peritonitis (1 case reported) 1
• Urticaria occurs in 1% of patients (95% CI 0-3%) 1

Predictors of Treatment Discontinuation

Women at highest risk for discontinuing dienogest due to metrorrhagia have the following characteristics: 2, 3

• Uterine size ≥6 cm in minor axis (significantly associated with discontinuation) 3
• Adenomyosis located in the anterior uterine wall (6 of 7 discontinuation cases had anterior wall involvement) 3
• Elevated baseline pain scores (higher dysmenorrhea VAS at baseline) 2
• Elevated serum CA-125 levels at baseline 2
• Lower baseline hemoglobin levels 2
• Type 1 adenomyosis (diffuse involvement) rather than type 2 (focal) 2

Clinical Implications for Safe Use

Dienogest can be safely administered when: 3

• Uterine size is <6 cm in the minor axis
• Main adenomyosis lesion is located in the posterior uterine wall
• Baseline hemoglobin is adequate to tolerate potential bleeding

For women with severe uterine enlargement (≥100 mm maximum dimension): 5

• Consider 4 months of GnRH agonist pre-treatment to reduce uterine size before initiating dienogest
• This approach allows dienogest to serve as effective maintenance therapy after GnRH agonist discontinuation

Long-Term Safety Profile

• 66.7% of patients can continue dienogest until menopause or for >80 months, demonstrating good long-term tolerability 2
• Long-term use does not significantly decrease serum estradiol levels, which may explain the favorable bone safety profile compared to GnRH agonists 2
• All laboratory parameters typically remain within normal ranges during extended treatment 5
• Dienogest is particularly well-tolerated in women with type 2 (focal) adenomyosis 2

Anti-Androgenic Effects

Dienogest has anti-androgenic properties, which should be considered in specific patient populations 6

• May worsen hypoandrogenism in women with low testosterone levels
• Could potentially affect libido or sexual function in susceptible patients
• This is particularly relevant in cancer survivors with iatrogenic premature ovarian insufficiency, though less applicable to typical adenomyosis patients 6

Monitoring Recommendations

• Assess hemoglobin levels at baseline and monitor for anemia development during treatment 4
• Measure uterine dimensions via transvaginal ultrasound before initiating therapy to predict bleeding risk 3
• Evaluate pain scores and serum CA-125 levels at baseline as potential predictors of treatment response and tolerability 2