Obesity in menopause care

We appreciate the letter by Allgayer and colleagues on the omission of obesity from our recently published European Society of Endocrinology Clinical Practice Guideline for Evaluation and Management of Menopause and the Perimenopause.1 We agree that it is a very important topic regarding its high prevalence (as Allgayer and colleagues indicated, according to the WHO 16% of adults were obese in 20222 with a higher prevalence in postmenopausal women3) and the fact that obesity impacts both menopausal symptoms (eg, body fat gains during the menopausal transition are associated with greater hot flash reporting4) and general health (eg, increased risk of cardiovascular disease [CVD], T2DM, and breast cancer5). In our guideline, we acknowledge that lifestyle factors such as obesity influence the occurrence of menopausal symptoms, their severity, and their treatment.1 However, as obesity is not a main focus of the guideline, we would like to take the opportunity with this response letter to express our view on obesity in (peri-/post) menopause in particular. Hormonal changes during menopause transition are associated with changes in energy expenditure and energy intake, inducing a positive energy balance leading to weight gain, in particular, increased abdominal fat deposition.6 Obese postmenopausal women are at increased risk of developing CVD,7 stroke,8 venous thromboembolism (VTE),9 and breast cancer10 compared to lean postmenopausal women. This does not necessarily mean that these women should be prevented from taking menopausal hormone therapy (MHT) but merely that special consideration should be given to baseline assessment (MHT indications and risks), selection of MHT regimen, and follow-up.5 Essential components and recommendations of clinical assessments prior to introduction of MHT are listed in Table 5 of our guideline1; in obese women we advise to give special attention to the following components5: Cardiovascular risk assessment: age, smoking, arterial hypertension, diabetes mellitus, dyslipidemia (for stroke: atrial fibrillation, left ventricular hypertrophy) VTE: family or personal history of VTE (provoked or unprovoked?), lifestyle factors, known thrombophilia Breast cancer: inherited gene mutations BRCA1/2, family history of breast cancer, personal history of benign breast disease, alcohol intake, past history of hormone therapy use, advanced age at first delivery, nulliparity, young age at menarche, late menopause, increased mammographic density It should be noted though that BMI affects breast cancer risk in women using combined MHT such that the absolute and relative excess risks associated with MHT use are greater for lean women than for obese women.11 If the decision is made to commence MHT, we advise that in women at increased risk of VTE or intermediate risk of CVD, a transdermal route of MHT administration is preferred.1,5 Since obese women are at increased baseline risk of both breast and endometrial cancer, the selection of the progestogen should be individualized. Alternatively, nonhormonal (eg, fezolinetant, elinzanetant, SSRIs12) and/or nonpharmacological therapies (eg, physical activity) may be used to relieve menopausal symptoms,1 but these have not been investigated specifically in obese women. As in nonobese women, the optimal duration of treatment with systemic MHT should be determined considering ongoing benefits, potential risks, and personal preferences. Currently, incretin-based therapies (eg, GLP-1 or dual GLP-1/GIP agonists) are receiving a lot of attention. In postmenopausal women with overweight or obesity treated with semaglutide, MHT use was associated with an improved weight loss response,13 and a recent small study reported superior total body weight loss in 40 women using MHT concurrently with tirzepatide (17%) vs. 80 women using tirzepatide alone (14%).14 More research with larger sample sizes is needed in this area to confirm these findings and to investigate underlying mechanisms of these differential weight loss responses. Although tirzepatide reduced bioavailability of combined oral contraception (COC),15 semaglutide, liraglutide, and dulaglutide did not seem to impact COC bioavailability,16-18 and there are no safety data on incretin-based therapies and MHT. Notably, we continue to support a holistic approach for care of women in menopause and would encourage all clinicians to manage obesity alongside any menopausal problems.1 Leonie van Hulsteijn (Writing—original draft [equal], Writing—review & editing [equal]), Irene Lambrinoudaki (Writing—review & editing [equal]), Olaf Dekkers (Writing—review & editing [equal]), Stephanie Faubion (Writing—review & editing [equal]), Angelica Lindén Hirschberg (Writing—review & editing [equal]), Channa Jayasena (Writing—review & editing [equal]), Yvonne Louwers (Writing—review & editing [equal]), JoAnn Pinkerton (Writing—review & editing [equal]), Antoan Stefan Sojat (Writing—review & editing [equal]), and Mary Ann Lumsden (Writing—review & editing [equal]) This response was developed independently and did not receive any financial support.