Estradiol and levonorgestrel side effects

What does the patient leaflet say about side effects?

From the patient leaflet: What is the most important information I should know about Climara Pro (a combination of estrogen and progestogen)?

Do not use estrogens with or without progestogens to prevent heart disease, heart attacks, strokes, or dementia (declines of brain function). Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older. Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia. Using estrogen-alone may increase your chances of getting strokes or blood clots. Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age and older. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia. Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Because other products and doses have not been studied in the same way, it is not known how the use of Climara Pro will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with Climara Pro.

What does the label list?

From the label: adverse reactions

The most common adverse reactions (≥5 percent) with Climara Pro are: application site reaction, vaginal bleeding, breast pain, upper respiratory infection, back pain, depression, pain, headache and flu syndrome.

Table 1: All Treatment Emergent Reactions Regardless of Relationship Reported at a Frequency of >3% with Climara Pro in the 1-year Endometrial Hyperplasia Study

Rows and numbers as the label prints them, under its own column headings (the first rows of a longer table where it runs on). A reaction in a trial table is not necessarily caused by the medicine, and trials differ from everyday use.

From the label: adverse reactions, continued

The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [ see Boxed Warning, Warnings and Precautions (5.1) ] Malignant Neoplasms [see Boxed Warning, Warnings and Precautions (5.2) ] The most common adverse reactions (≥5 percent) with Climara Pro are: application site reaction, vaginal bleeding, breast pain, upper respiratory infection, back pain, depression, pain, headache and flu syndrome. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-84-BAYER (1-888-842-2937) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below is from a one-year, prospective, multicenter, double blind, double dummy, randomized, controlled trial investigating the effect of three different dosage combinations of E 2 /LNG versus E 2 alone on the development of endometrial hyperplasia. All women were postmenopausal, had a serum estradiol level of less than 20 pg/mL, and the sample included both symptomatic and asymptomatic women. …

What do FAERS reports show?

2,021 reports list estradiol and levonorgestrel among the medicines taken, each a report of something that happened, not proof the medicine caused it; 1 are coded as a death and 14 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is. Of the 18 reactions below, 5 are named by the same term (in US spelling) in the label's adverse reactions, warnings or patient leaflet; a reaction the label does not name may still be there under another word, and a report does not show that the medicine caused it.

Reports received each year

• 118
• 239
• 159
• 101
• 95
• 89
• 71
• 90
• 96
• 124
• 60

• 2016
• 2017
• 2018
• 2019
• 2020
• 2021
• 2022
• 2023
• 2024
• 2025
• 2026

The 25 most reported reactions

• Product Adhesion Issue668
• Product Physical Issue329
• Wrong Technique In Product Usage Process (a use or a product term, not a reaction)259
• Device Adhesion Issue245
• Hot Flush (named in the label)226
• Application Site Rash189
• Drug Ineffective (a use or a product term, not a reaction)156
• Product Quality Issue (a use or a product term, not a reaction)134
• Application Site Pruritus107
• Application Site Erythema98
• Device Breakage92
• Application Site Irritation89
• Drug Dose Omission (a use or a product term, not a reaction)87
• Vaginal Haemorrhage73
• Wrong Technique In Device Usage Process (a use or a product term, not a reaction)71
• Headache (named in the label)61
• Insomnia (named in the label)58
• Product Use Issue (a use or a product term, not a reaction)57
• Postmenopausal Haemorrhage55
• Uterine Haemorrhage55
• Metrorrhagia51
• Rash (named in the label)51
• Feeling Abnormal45
• Night Sweats (named in the label)43
• Incorrect Dose Administered (a use or a product term, not a reaction)41

What next?

Estradiol and levonorgestrel: the full record

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