Mounjaro (tirzepatide) and Depo-Provera (depot medroxyprogesterone acetate) are commonly prescribed medications that some individuals may use concurrently. Mounjaro is a dual GIP/GLP-1 receptor agonist licensed for type 2 diabetes and weight management, whilst Depo-Provera is a long-acting injectable contraceptive administered every 12–13 weeks. Understanding how these medications interact—and the practical considerations when using them together—is essential for safe and effective treatment. This article examines the compatibility of Mounjaro and Depo-Provera, addressing contraceptive efficacy, weight management, and when to seek medical advice.

What Are Mounjaro and the Depo-Provera Injection?

Mounjaro (tirzepatide) is a prescription medicine licensed in the UK for the treatment of type 2 diabetes mellitus and for weight management in adults with obesity or overweight with weight-related comorbidities. It belongs to a class of medications known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. Mounjaro works by mimicking natural hormones that regulate blood sugar levels and appetite. It enhances insulin secretion when blood glucose is elevated, suppresses glucagon release, slows gastric emptying, and reduces appetite—leading to improved glycaemic control and significant weight loss in many patients.

Mounjaro is administered as a once-weekly subcutaneous injection, with doses typically starting at 2.5 mg as an initiation dose (not for glycaemic/weight control), with escalation typically every 4 weeks to maintenance doses (5-15 mg) based on individual response and tolerability. Common side effects include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and constipation, particularly during dose escalation. More serious but rare adverse effects can include pancreatitis, gallbladder disease (cholelithiasis/cholecystitis), and hypoglycaemia when used with other glucose-lowering medications. Mounjaro is not recommended during pregnancy or breastfeeding and should be discontinued at least 1 month before a planned pregnancy. Caution is needed in patients with diabetic retinopathy, especially when used with insulin, and patients should be advised about the risk of dehydration and acute kidney injury.

Depo-Provera (depot medroxyprogesterone acetate, or DMPA) is a long-acting, reversible hormonal contraceptive commonly referred to as the "contraceptive injection." It is administered as an intramuscular injection every 12–13 weeks and works primarily by inhibiting ovulation through suppression of gonadotrophin release. It also thickens cervical mucus and alters the endometrial lining, providing highly effective contraception that is over 99% effective when used correctly.

Depo-Provera is widely used in the UK and is particularly suitable for individuals who prefer a method that does not require daily adherence. However, it is associated with several side effects, including irregular menstrual bleeding (which may progress to amenorrhoea), weight gain, mood changes, and a temporary reduction in bone mineral density with prolonged use. Return to fertility may be delayed for up to a year after stopping the injection. The Faculty of Sexual and Reproductive Healthcare (FSRH) recommends that healthcare professionals discuss these risks, particularly regarding bone health in adolescents and women over 45 years. Regular review of long-term use is advised, along with lifestyle advice for bone health.

Patients are encouraged to report any suspected side effects from either medication via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

Can You Use Mounjaro and Depo-Provera Together?

There is no official contraindication to using Mounjaro and Depo-Provera concurrently, and no direct pharmacological interaction between tirzepatide and medroxyprogesterone acetate has been identified in clinical studies or regulatory guidance. Both medications act through distinct mechanisms—Mounjaro primarily affects glucose metabolism and appetite regulation, while Depo-Provera modulates reproductive hormones to prevent ovulation. As such, they do not interfere with each other's primary pharmacological actions at a molecular level.

However, there are important practical considerations when using these medications together. One key concern relates to gastrointestinal effects. Mounjaro slows gastric emptying, which can affect the absorption of oral medications. According to the MHRA Summary of Product Characteristics (SmPC), tirzepatide can reduce exposure to oral contraceptives, and additional barrier contraception is recommended for 4 weeks after initiation and each dose increase. Depo-Provera, being an injectable contraceptive, bypasses the gastrointestinal tract entirely, so its contraceptive efficacy is not compromised by delayed gastric emptying. This makes it an option that avoids gastrointestinal absorption concerns for individuals taking GLP-1 or dual GIP/GLP-1 receptor agonists.

Another consideration is weight change. Depo-Provera is associated with weight gain in some users, though individual responses vary considerably. Conversely, Mounjaro typically promotes weight loss, particularly when used for obesity management. The net effect on body weight when using both medications will depend on individual metabolic responses, lifestyle factors, and the primary indication for Mounjaro use.

Patients should be reassured that using these medications together does not reduce the effectiveness of contraception, provided Depo-Provera injections are administered on time every 12-13 weeks. If you experience severe gastrointestinal side effects from Mounjaro—such as persistent vomiting—it is important to contact your GP, though this would not directly affect Depo-Provera's contraceptive action. Always inform all prescribers about every medication you are taking to ensure comprehensive care and monitoring.

Managing Weight Loss and Hormonal Contraception

Weight management is a common concern for individuals using hormonal contraception, particularly Depo-Provera, which has a documented association with weight gain. The mechanism behind this is not fully established, with various hypotheses including potential effects on appetite, fluid retention, and metabolic changes, though evidence is mixed and responses vary significantly between individuals.

When Mounjaro is prescribed—whether for type 2 diabetes or weight management—it often leads to substantial weight reduction. Clinical trials have demonstrated that tirzepatide can result in significant weight loss in individuals with obesity, with effects varying by dose and individual factors. The weight loss effects may be smaller in people with type 2 diabetes compared to those using it primarily for weight management. This weight loss occurs through multiple mechanisms: reduced appetite and caloric intake, delayed gastric emptying leading to prolonged satiety, and effects on energy expenditure and fat metabolism.

For individuals using both medications, the weight-loss effects of Mounjaro may help offset weight concerns associated with Depo-Provera, though individual responses will vary considerably. It's important to maintain realistic expectations and focus on monitoring and shared decision-making with your healthcare team rather than assuming one medication will fully counteract effects of another.

Monitoring and support are essential. Regular follow-up appointments allow healthcare professionals to:

• Assess weight trends and metabolic parameters (HbA1c, lipids, blood pressure)

• Monitor for adverse effects from either medication

• Adjust Mounjaro dosing as needed for optimal efficacy and tolerability

• Consider reducing insulin or sulfonylurea doses when initiating or increasing Mounjaro to reduce hypoglycaemia risk

• Ensure Depo-Provera injections are administered on schedule

• Provide nutritional counselling and lifestyle advice

Patients should maintain realistic expectations about weight loss and understand that individual responses vary. Some may experience significant weight reduction, while others may see more modest changes. If pregnancy is planned in the future, remember that Mounjaro should be discontinued at least 1 month before attempting conception, and return to fertility after stopping Depo-Provera may take up to a year. Open communication with your healthcare team about your goals, concerns, and any side effects is crucial for achieving the best outcomes with both medications.

When to Speak with Your GP or Healthcare Professional

While using Mounjaro and Depo-Provera together is generally considered safe, certain situations warrant prompt medical attention. Understanding when to seek advice ensures both medications are used safely and effectively.

Contact your GP or healthcare professional if you experience:

• Severe or persistent gastrointestinal symptoms: While nausea, vomiting, and diarrhoea are common when starting or increasing Mounjaro doses, severe or prolonged symptoms—especially if accompanied by dehydration, inability to keep fluids down, or severe abdominal pain—require medical assessment.

• Signs of pancreatitis: Severe, persistent upper abdominal pain (often radiating to the back), nausea, and vomiting may indicate acute pancreatitis, a rare but serious side effect of GLP-1 and GIP receptor agonists. This requires immediate medical evaluation—call NHS 111 for urgent advice or go to A&E if symptoms are severe.

• Unexpected or concerning bleeding patterns: While irregular bleeding is common with Depo-Provera, particularly in the first few months, any unusually heavy, prolonged, or concerning bleeding should be discussed with your healthcare professional to rule out other causes.

• Symptoms of ectopic pregnancy: Although Depo-Provera is highly effective, no contraceptive is 100% reliable. Severe abdominal or pelvic pain, especially if accompanied by vaginal bleeding, dizziness, or shoulder pain, could indicate ectopic pregnancy and requires urgent assessment—call 999 or go to A&E immediately.

• Significant mood changes: If you experience notable changes in mood or symptoms of depression, discuss these with your GP. While both medications have been associated with mood effects in some individuals, the evidence for direct causality is limited.

• Concerns about weight or metabolic health: If you are not achieving expected weight loss on Mounjaro, or if you experience unexpected weight gain despite treatment, your healthcare professional can review your treatment plan, assess adherence, and consider alternative approaches.

Routine monitoring is also important. Ensure you attend scheduled appointments for Depo-Provera injections (every 12–13 weeks) and follow-up visits for Mounjaro dose adjustments and monitoring of diabetes control or weight loss progress. Your healthcare team can provide personalised advice based on your individual health status, treatment goals, and response to therapy. Never hesitate to raise questions or concerns—your safety and wellbeing are the priority, and open communication with your healthcare professionals ensures the best possible outcomes when using these medications together.

Frequently Asked Questions