Can weight loss drugs make contraception and HRT less effective?
Have you seen the 'Ozembic baby' tagline on social media? Do weight loss drugs affect contraception, and if so, what does it mean for other hormonal therapies like HRT?
When you look up the ‘Ozempic baby’ tagline on TikTok, you’ll see cases of women experiencing unexpected pregnancies while on weight loss medications like Ozempic.
Do these drugs decrease the effectiveness of contraception? Do you need to change your contraception method if you are taking Ozempic? And for the providers in the room, how should we counsel patients when you are prescribing these medications?
I counselled Dr Aaron Lazorwitz (Complex Family Planning OBGYN at Yale), looked up drug labels and literature to find the answers. Let’s dive in.
Weight Loss Drugs
Let’s start with a quick recap of what the weight loss drugs are. The names you probably came across are Ozempic, Wegovy, Zepbound and Mounjuro.
They were initially developed and approved for type 2 diabetes. Further research has then demonstrated that they can lead to 15-20% of body weight loss in trials, significantly outperforming previously available weight loss medications. With that data, these drugs gained approvals as obesity treatments.
Generally, these medications are prescribed for adults with:
A body mass index (BMI) of 30 or greater
A BMI of 27 or greater with at least one weight-related health condition
There has been a steep increase in demand for these medications lately, especially as they became more accessible for those willing to pay out of pocket. The costs are not insignificant and many insurance plans do not yet cover them for weight loss. Manufacturers have significantly ramped up production to meet demand. Novo Nordisk reported that at least 25,000 people in the US are now starting Wegovy each week1.
How do weight loss drugs work?
TL;DR: They decrease appetite and slow down the emptying of the stomach (‘gastric emptying’) which makes people feel more full after a meal so overall people feel less hungry and eat less.
After eating a meal, our bodies break down the food into nutrients that are then absorbed and used for energy. Two important hormones in this process are GIP (Gastric Inhibitory Polypeptide) and GLP-1 (Glucagon-Like Peptide-1). They belong to a group of hormones that help regulate blood sugar levels (also called incretins). They are naturally released in our bodies in the gastrointestinal tract in response to eating. GIP mainly helps reduce blood sugar levels after a meal while GLP-1 slows down gastric emptying and reduces appetite.
Weight loss medications act as receptor agonists of these hormones. A receptor agonist is a substance that binds to a specific receptor in the body and activates it, mimicking the action of a naturally occurring hormone.
The active ingredient in Ozempic and Wegovy is called semaglutide - GLP1 receptor agonist. This means that the drug mimics the action that the hormone GLP1 would have on your body - it slows down gastric emptying, which makes you feel full longer and helps to reduce appetite and caloric intake. Both drugs are approved for people with Type 2 Diabetes and Wegovy is also approved for people with obesity or those who are overweight and have health problems related to excess weight.
The active ingredient in Zepbound and Mounjuro is called tirzepatide - it has a dual action as a GIP and GLP-1 receptor agonist. Tirzepatide is also approved for Type 2 Diabetes as it’s been shown to improve glycaemic control.
Weight Loss Drugs and Contraception
The primary concern about weight loss drugs and contraception is that they may affect the absorption and effectiveness of oral contraceptives, including COCPs, POPs and plan B pills.
Delayed Gastric Emptying
The proposed mechanism in which weight loss drugs decrease the effectiveness of oral contraceptives is via the delay in gastric emptying.
It’s been suggested that tirzepatides had a greater impact on the absorption of oral hormonal contraceptives than semaglutides. Currently, only Mounjaro carries a warning about birth control pill effectiveness on its label:
“Advise females using oral contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation. Use of Mounjaro may reduce the efficacy of oral hormonal contraceptives due to delayed gastric emptying. This delay is largest after the first dose and diminishes over time.”
This is based on their study which showed a 20% reduction in the overall exposure of combined oral contraceptive with ethinyl estradiol and norgestimate, observed following the administration of a single 5 mg dose of Mounjaro.
Although the label suggests that the drop in serum drug levels for contraceptives seems to resolve after a few weeks, the research is limited. Every person may react differently depending on the doses of their weight loss drug and contraceptive pill as well as their individual metabolism and pharmacokinetics.
So if you are on a combined contraceptive pill or a mini pill as your regular birth control method and are taking Mounjaro or Zepbound, there are two options if your goal is effective pregnancy prevention:
Adding another protection such as a barrier method (condoms).
Alternatively, it may be preferable to switch the contraceptive method to another one if possible (for example IUD, implant, DMPA).
Nausea and Vomiting
Another way in which these weight loss medications may impact the effectiveness of contraceptive methods is via the unpleasant gastrointestinal side effects. All weight loss medications can cause nausea and vomiting, particularly during the initial stages of treatment. If vomiting occurs within a few hours of taking an oral contraceptive pill, it can compromise the pill's effectiveness. Usually, if someone experiences nausea and vomiting regularly, it would not be recommended to use oral contraceptive pills as a first-line option.
Weight Loss and Fertility
So do we think that the cases of “Ozempic babies” are due to the above mechanisms? Potentially. However, there’s another mechanism that might be an even more probable explanation.
Healthy weight and lifestyle are very important for optimal fertility. Women who are overweight have elevated levels of estrogen (adipose tissue is a significant site for estrogen production) and insulin resistance. Elevated estrogen levels can lead to various menstrual disorders, including oligomenorrhea (infrequent periods), amenorrhea (absence of periods), and heavy menstrual bleeding. This means that overweight women may not ovulate regularly and can struggle with their fertility.
Weight loss medications help achieve a healthy weight and hence they can also stabilize estrogen levels. This will help regulate patient’s menstrual cycles, improve rates of ovulation and thereby increase their chances of getting pregnant. Research is underway to explore this potential to boost ovulation in women with obesity and PCOS. This is probably the mechanism which explains the anecdotes and social media reports of ‘Ozempic babies’.
The FDA recommends stopping these medications at least 2 months before you start trying to get pregnant. If you do get pregnant while taking ANY of these weight loss medications, talk with a physician right away as it may not be safe to continue them.
Weight and Contraception
It’s also important to note that weight and BMI are important considerations when choosing contraception in the first place. There is some evidence that certain hormonal birth control methods may be less effective in obese and overweight women.
The method that is most important to talk about here is the hormonal patch. It’s a combined hormonal method in the form of a small patch that is applied on the skin. The patch releases a steady dose of hormones through the skin into the bloodstream. There are two brands of patches: ORTHO EVRA and TWIRLA. Results of clinical trials suggest that ORTHO EVRA may be less effective in women with body weight ≥198 lbs. (90 kg). TWIRLA is actually contraindicated in women with a BMI ≥ 30 as it was proven in clinical studies to have reduced effectiveness. The FDA drug labels for both patches recommend that obese patients do not rely on the patch for contraception.
Dr Lazorwitz explained to me the theory behind the mechanism of this. People with higher BMI have greater sequestration of steroid hormones in fat tissue, and so less free hormones to act as contraception in the body. So with a method like the patch where skin absorption is the primary absorption method, it seems the absorption of hormones is interfered with and causes likely lower drug levels and reduced efficacy.
Moreover, the risk of blood clots rises as BMI increases over 30 and rises further with BMI over 35. So depending on other cardiovascular risk factors (high cholesterol, high sugar, diabetes and others), the medical risk may outweigh the benefits of using hormonal combined methods. This is a particularly difficult balance and decision to make for patients with PCOS who may be overweight but are using combined methods to manage their symptoms.
Weight loss drugs and Hormone Replacement Therapy
What about perimenopausal and menopausal patients taking hormone replacement therapy (HRT)? Do weight loss drugs have an impact on HRT?
Women going through perimenopause and menopause have declining estrogen levels. This impacts the body and health profoundly and is a story for another article. In the context of weight loss drugs, it’s important to note that a decline in estrogen puts women at risk of:
weight gain,
osteoporosis and bone fracture,
developing type 2 diabetes and cardiovascular diseases (CVD).
Weight loss drugs can certainly help patients who are putting on weight during the peri/menopausal period. They may also have a positive effect on lowering the risk of developing diabetes and CVD. Some studies have demonstrated synergistic benefits of using HRT and GLP1 agonists like Ozempi. In postmenopausal women with overweight or obesity treated with these weight loss medications, HRT use was associated with improved weight loss2.
It’s also important to take into consideration the impact on bone health and fracture risk when thinking about HRT and weight loss drugs. Both obesity and rapid weight loss can negatively impact bone health. However, the exact effects of weight loss drugs on bone metabolism, bone health and fracture risk are not yet clear. The research on the effects of taking HRT and weight loss drugs together is still quite limited.
Making an Informed Decision
There are many factors to consider to make an informed decision about contraception, HRT and weight loss medications.
With the current public attention given to the dramatic weight loss achieved with these weight loss medications, patients are seeking them out from many potential sources, including online prescribers. It’s now possible to receive a prescription with minimal direct interaction with a healthcare provider. This means that there’s probably limited opportunity to discuss the impacts of these medications on all aspects of life, including fertility, and make an informed decision.
Additionally, as research is limited and still in development, some healthcare providers prescribing these weight loss medications may be unaware of how these medications affect reproductive health, particularly as to how they must be stopped well before pregnancy due to safety concerns. Thus, we end up with a double-edged sword situation of women taking these weight loss medications unintentionally becoming pregnant due to improved fertility and having to then suddenly discontinue their weight loss medicine due to the pregnancy itself.
Final Thoughts
Based on how interdependent various hormonal mechanisms are in our bodies, the possible interactions between contraception, HRT and weight loss drugs are not surprising. Given that we now have a lot of tech-enabled players in the market providing these medications, I’m hoping that we will soon see some insights from real-world data on these effects and interactions.
https://edition.cnn.com/2024/05/02/health/wegovy-weight-loss-drug-new-prescriptions/index.html