What causes vaginal bleeding with hormonal pellet (hormone replacement therapy) therapy?

From the Guidelines

Hormonal pellet users experiencing vaginal bleeding should be managed on a case-by-case basis, with consideration of their individual goals and medical history, and treatment options may include NSAIDs, hormonal treatment, or antifibrinolytic agents, as needed, according to the 2024 U.S. Selected Practice Recommendations for Contraceptive Use 1.

Management of Vaginal Bleeding

The management of vaginal bleeding in patients using hormonal pellets involves exploring patient goals, including continued method use or method discontinuation, and providing reassurance and advice on managing bleeding irregularities.

• If the patient wants to continue use, the provider should provide reassurance and advise the patient that they may contact their provider at any time to discuss bleeding irregularities or other side effects.
• If the patient desires removal or discontinuation of the method at any time, the method should be removed (if applicable), and counseling on alternative contraceptive methods should be offered, with initiation of another method if desired.

Treatment Options

Treatment options for vaginal bleeding in hormonal pellet users may include:

• NSAIDs, 5–7 days, for spotting or light bleeding
• Hormonal treatment, such as low-dose combined oral contraceptives or estrogen, 10–20 days, for heavy or prolonged bleeding
• Antifibrinolytic agents, such as tranexamic acid, 5 days, for heavy or prolonged bleeding It is essential to consider the patient's preferences, treatment goals, and medical history when selecting a treatment option, as recommended by the 2024 U.S. Selected Practice Recommendations for Contraceptive Use 1.

Underlying Health Conditions

If clinically indicated, an underlying health condition, such as interactions with other medications, sexually transmitted infections, pregnancy, thyroid disorders, or new pathologic uterine conditions (e.g., polyps or fibroids), should be considered and treated or referred for care, as stated in the 2024 U.S. Selected Practice Recommendations for Contraceptive Use 1.

From the FDA Drug Label

In cases of breakthrough bleeding, as in all cases of irregular bleeding per vaginum, nonfunctional causes should be borne in mind and adequate diagnostic measures undertaken. Because of its prolonged action and the resulting difficulty in predicting the time of withdrawal bleeding following injection, medroxyprogesterone acetate is not recommended in secondary amenorrhea or dysfunctional uterine bleeding. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy

Hormonal Pellet Vaginal Bleeding:

• Medroxyprogesterone acetate can cause breakthrough bleeding and irregular bleeding.
• In cases of abnormal vaginal bleeding, it is essential to rule out malignancy and consider nonfunctional causes.
• The drug is not recommended for secondary amenorrhea or dysfunctional uterine bleeding due to its prolonged action and difficulty in predicting withdrawal bleeding 2 2.

From the Research

Hormonal Pellet Vaginal Bleeding

• Hormonal replacement therapy (HRT) is known to cause abnormal vaginal bleeding in some women, which can be a reason for discontinuation of the therapy 3.
• The mechanisms of this bleeding are not well understood and do not correlate well with endometrial histology or the type or dose of hormone therapy used 3.
• Potential mechanisms involved in endometrial bleeding include changes in the ratio of vascular endothelial growth factor to thrombospondin-1, alterations in matrix metalloproteinases and their tissue inhibitors, changes in endometrial haemostasis due to tissue factor, and increased endometrial leucocytes 3.

Management of Abnormal Uterine Bleeding

• Abnormal uterine bleeding (AUB) in women taking HRT is a common problem that requires investigation to rule out organic causes, including endometrial cancer 4.
• The main functional causes of AUB in women taking HRT are resumption of ovarian activity, poor compliance, and trophic disorders of the endometrium 4.
• Pelvic ultrasound can be used to measure endometrial thickness, and a thickness of less than or equal to 4mm may indicate that further uterine exploration is not necessary in the case of a single episode of AUB 4.
• However, recurrent AUB or an endometrial thickness greater than 4mm may require additional uterine investigations, such as hysteroscopy and histology 4.

Diagnostic Techniques

• Transvaginal uterine ultrasound and endometrial biopsy are two diagnostic techniques that can be used to evaluate the endometrium of postmenopausal women taking HRT 5.
• However, the results of ultrasound as a screening technique do not correlate well with the results of endometrial biopsy, and unscheduled bleeding should be investigated regardless of the results of ultrasonographically determined endometrial thickness 5.
• Ultrasound assessment of endometrial thickness and endometrial polyps can also be used to evaluate the endometrium in postmenopausal women on HRT 6.

Management of Common Problems

• Common problems associated with HRT, including vaginal bleeding, can often be managed by changing the dose, using another preparation or regimen, or altering the route of administration 7.
• Irregular bleeding warrants endometrial biopsy to rule out hyperplasia, and gynecologic referral is recommended when endometrial biopsy is necessary or when symptoms fail to respond to adjustments in hormone therapy 7.