GLP-1S AND HRT
What clinicians need to know about absorption, safety and patient counselling
DR MUNINDER WALIA
Dr Muninder Walia is the founder of Private Medical Service, a private GP clinic run from Berkshire Grove Hospital in Maidenhead. Accredited by the British Menopause Society, she has a particular interest and expertise in women’s health, with a special focus on menopause care. She is also a member of the Primary Care Women’s Health Society, European Menopause and Andropause Society, and the International menopause society.
Aesthetics has seen two major shifts in recent years – one towards women’s health and menopause and the other towards health and wellness. More recently this has seen the convergence of two major therapeutic tools – hormone replacement therapy (HRT) and GLP-1receptor agonists. As more midlife women seek support for menopausal symptoms while also using GLP-1s for weight management or metabolic health, clinicians must understand how these treatments intersect.
HOW GLP-1S ALTER GUT PHYSIOLOGY
GLP-1 receptor agonists such as semaglutide and tirzepatide act directly on gut hormones. They work in three principal ways:
1. Delayed gastric emptying – by reducing stomach contractions and suppressing gastric motility.
2. Altered intestinal transit – slowing movement through the small intestine, where most oral drugs are absorbed.
3. Gastrointestinal side effects – including nausea and vomiting, which can reduce or eliminate effective drug absorption. Dr Muninder Walia, GP, British Menopause Society-accredited menopause specialist and founder of Private Medical Service, explains, “From a physiological standpoint, you’re slowing down the gastric emptying, altering intestinal motility. That can have huge effects on oral medication.”
For most drugs, this may mean delayed onset of action. But for hormone therapy – where consistency and predictability are essential – this variability raises specific concerns.
WHY ORAL HRT IS PARTICULARLY AFFECTED
The British Menopause Society has highlighted concerns regarding oral HRT in women using GLP-1s. The reason is simple: oral oestrogen and progesterone must pass through the gastrointestinal tract and be absorbed in the small bowel.
Delayed gastric emptying means tablets remain in the stomach longer before reaching the absorption site. Vomiting may reduce bioavailability entirely. Even without overt symptoms, absorption can become inconsistent.
As Dr Walia notes, “The absorption becomes delayed or less predictable because you don’t know how much is actually being absorbed… During periods of nausea and vomiting, you’re either losing the drug or partially losing it.”
While transdermal preparations bypass the gut entirely, oral preparations do not.
EXTRAPOLATING FROM CONTRACEPTIVE DATA – WITH CAUTION
Evidence from Eli Lilly’s tirzepatide studies demonstrated reduced bioavailability of oral contraceptives, particularly during initiation and dose escalation phases. Barrier contraception was recommended for four weeks after starting or increasing the dose.
However, as Dr Walia emphasises, extrapolating this data directly to oral HRT has limitations: “This gets to the limits of what we can and what we can’t legitimately extrapolate from contraceptive data to HRT”, she says.
The difference lies in clinical feedback. Oestrogen under-absorption is often symptomatic – hot flushes, night sweats and mood symptoms may recur. Progesterone under-absorption, however, is far more concerning.
WHY PROGESTERONE IS THE SILENT RISK
In women with an intact uterus, progesterone provides endometrial protection. Unlike oestrogen deficiency, inadequate progesterone does not produce obvious symptoms. “Progestogen failure is silent, but it’s dangerous,” Dr Walia warns.
Reduced oral progesterone absorption may lead to insufficient endometrial protection, increasing the risk of hyperplasia. This is why the progesterone component is considered the primary concern when GLP-1s are introduced.
CLINICAL RED FLAGS AND PRACTICAL MANAGEMENT
In real-world practice, what should clinicians monitor? Dr Walia recommends:
• Documenting baseline bleeding patterns clearly
• Reviewing bleeding with every GLP-1 dose escalation
• Treating any new bleeding pattern as significant
• Maintaining a low threshold for switching to non-oral progestogen options. She describes the levonorgestrel intrauterine system (LNG-IUS), such as the Mirena coil, as “the most defensible risk management strategy” in this context The LNG-IUS:
• Bypasses first-pass metabolism
• Provides consistent endometrial protection
• Is licensed for menopausal use (Mirena)
• Offers a low-maintenance solution
It can be considered particularly in women with obesity and additional endometrial risk factors, significant GI symptoms on GLP-1s, prior bleeding concerns, or those requiring higher oestrogen doses.
THE DIAGNOSTIC CHALLENGE: OVERLAPPING SYMPTOMS
Another complexity lies in symptom interpretation. GLP-1s commonly cause bloating, reflux, constipation, nausea and altered appetite – all symptoms that overlap with menopause or HRT side effects.
As Dr Walia explains, “GLP-1 receptor agonists can blur the clinical picture in menopausal women because many of their predictable gut effects overlap almost exactly with menopausal symptoms.”
The key to differentiation is temporal patterning. GLP-1 side effects often coincide with dose initiation or escalation. Menopausal symptoms tend to follow a more gradual trajectory. Weight loss itself can also alter gut microbiota and symptom perception, adding another layer of complexity.
WHAT HAPPENS WHEN GLP-1S ARE STOPPED?
Discontinuation introduces yet another variable.
Gut motility typically normalises over six to eight weeks. Appetite returns – sometimes abruptly. Bleeding patterns may shift. Oral HRT absorption becomes more predictable again.
But here lies the paradox: if HRT doses were increased to compensate for impaired absorption during GLP-1 use, those higher doses may now become excessive once normal gut function resumes.
As Dr Walia summarises, “In menopausal women, stopping GLP-1 therapy can unmask higher effective HRT doses… the tolerability profiles and bleeding profiles will be altered.”
This reinforces the need for active review during initiation, titration and discontinuation phases.
THREE ESSENTIAL QUESTIONS FOR CLINICIANS
Given that GLP-1s and HRT may be prescribed by different providers, communication gaps are common. Dr Walia recommends clinicians routinely ask: 1. Are you taking any weight-reducing medications? 2. What contraception are you using? 3. What type of HRT are you on (or considering)? Medication history must now explicitly include GLP-1 therapy. As Dr Walia notes, even anaesthetists are beginning to screen for weight-reducing drugs due to their impact on gastric emptying A shared-care approach is essential. Women should be informed about oral versus transdermal options, cancer risk discussions, thrombotic considerations and cost constraints within the NHS.
EVIDENCE GAPS AND FUTURE RESEARCH
Despite growing use, the evidence base remains limited.
Dr Walia highlights the need for prospective studies examining HRT pharmacokinetics during GLP-1 initiation, titration and cessation, clear data on oral progesterone exposure while using GLP-1s and safety studies to move from “physiologydriven caution” to “data-driven guidance”.
Current guidance, she notes, is risk-based rather than fully evidence-based.
A FINAL REASSURANCE – AND CAUTION
For clinicians counselling women, Dr Walia offers both reassurance and warning:
“Menopausal symptoms can still be well controlled and HRT can be safely adapted using strategies that bypass the gut.”
But she cautions: “Oral progestogen absorption may be unreliable while on GLP-1therapy, and insufficient exposure can affect the womb lining silently, so any new bleeding or spotting should be reported promptly.”
THE BOTTOM LINE
The intersection of GLP-1 therapy and menopause care is no longer niche. It is mainstream. For clinicians, the priorities are:
• Understand altered gut physiology
• Recognise the silent risk of progesterone under-absorption
• Favour transdermal or intrauterine strategies when appropriate
• Monitor bleeding proactively
• Review therapy during GLP-1 initiation, escalation and discontinuation As weight management pharmacotherapy expands, menopause care must evolve alongside it. The solution is not alarmism – but informed, individualised, evidence-seeking practice.