Can Zepbound (tirzepatide) cause menstrual irregularities, such as a period restarting, in women?

Zepbound (Tirzepatide) and Menstrual Irregularities

Yes, Zepbound (tirzepatide) can cause menstrual irregularities, including restarting periods, in women. While not extensively documented in clinical trials, there is evidence supporting that weight loss medications like tirzepatide can affect menstrual cycles through multiple mechanisms.

Mechanisms of Menstrual Changes with Tirzepatide

Weight Loss Effects

• Rapid weight loss from tirzepatide can disrupt hormonal balance, affecting the hypothalamic-pituitary-ovarian axis
• Changes in body fat percentage alter estrogen production, as adipose tissue is a significant source of estrogen in women
• The 10mg and 15mg doses of tirzepatide produce significant weight reductions (-10.1% and -13.2% respectively) 1, which may be sufficient to affect menstrual cycles

Direct Hormonal Effects

• Tirzepatide acts on GLP-1 and GIP receptors, which can indirectly influence reproductive hormones
• These receptors are present in the hypothalamus, which controls the release of gonadotropin-releasing hormone (GnRH)

Medication Interactions

• Tirzepatide significantly reduces the absorption of oral hormonal contraceptives 2
• This can lead to breakthrough bleeding or unexpected menstrual cycles in women using hormonal birth control

Clinical Presentation of Menstrual Changes

Women taking Zepbound may experience:

• Restarting of previously absent periods
• Changes in menstrual flow (heavier or lighter)
• Irregular timing of menstrual cycles
• Breakthrough bleeding
• Changes in cycle length (shorter or longer)

Risk Factors for Menstrual Irregularities

Certain women may be more susceptible to menstrual changes while on tirzepatide:

• Those with pre-existing menstrual irregularities
• Women with polycystic ovary syndrome (PCOS) 3
• Women with significant insulin resistance
• Those experiencing rapid weight loss
• Women using hormonal contraceptives

Management Considerations

For women experiencing menstrual irregularities on Zepbound:

1. Documentation and Monitoring

   • Track menstrual changes to establish patterns
   • Monitor for excessive bleeding or severe symptoms

2. Contraception Considerations

   • Consider non-oral contraceptive methods if using for birth control
   • IUDs may be preferable as they are not affected by tirzepatide's impact on absorption 2

3. Dose Adjustments

   • Slower dose escalation may reduce hormonal fluctuations
   • Lower maintenance doses may minimize menstrual disruptions

4. Evaluation of Abnormal Bleeding

   • Persistent or severe menstrual irregularities warrant further investigation
   • Rule out other causes of abnormal uterine bleeding

Important Caveats

• Menstrual irregularities are often temporary and may resolve as the body adjusts to the medication
• The benefits of weight loss and improved metabolic health may outweigh temporary menstrual changes
• In women with PCOS, weight loss from tirzepatide may actually improve menstrual regularity over time
• Case reports suggest tirzepatide may also affect sexual function in women 4, which could be related to hormonal changes

When to Seek Medical Attention

Women should consult their healthcare provider if experiencing:

• Extremely heavy bleeding
• Severe pelvic pain
• Prolonged menstrual irregularities (>3 months)
• Concerning symptoms such as fever, unusual discharge, or severe fatigue

Menstrual irregularities with tirzepatide are generally not dangerous but represent the body's hormonal adaptation to both the medication and resulting weight loss. Most changes are temporary and resolve with continued treatment or after discontinuation of the medication.