Semaglutide's Impact on Vaginal Health Explored

Semaglutide is a medication used for people with diabetes to help manage blood sugar and insulin levels, and for weight loss, used via injection.

Ozempic, Wegovy and Rybelsus are brand names for the ingredient semaglutide. Off-label uses for Wegovy, Ozempic, and Rybelsus include weight loss¹.

Semaglutide is readily available in the USA through online pharmacies and weight loss clinics without prescription or medical oversight. The drug is enthusiastically promoted on social media by fans, for whom it has made weight loss achievable².

Gut, hormonal, vaginal and urinary tract side-effects of semaglutide

Common listed side effects of Wegovy, Ozempic and Rybelsus include nausea, vomiting, diarrhoea, abdominal pain and constipation³.

However, there is a growing body of anecdotal evidence from some users of semaglutide (not listed by the manufacturer) of endocrine disruption and urogenital symptoms.

Some users report menstrual irregularities such as erratic/delayed periods, while others discuss an increase in recurrent yeast infections and disrupted vaginal flora.

Some users are reporting a surge in infections like BV, yeast and UTIs that they haven’t had in ‘years’, which only started after the commencement of semaglutide.

These users report increased recurrent yeast infections, bacterial vaginosis, urinary tract infections, or urinary tract symptoms that suggest infection, such as increased frequency or urgency.

Other user-reported impacts on the vulva and vagina of semaglutide include burning, sensitivity, dryness and impacts on libido. It’s unclear why these side effects occur while using the drug.

It is known that vaginal yeast infections are more common in diabetics and those with blood sugar dysregulation, including those on medication⁴, but this does not account for the reported urogenital and hormonal side effects experienced by semaglutide users, many of whom are not diabetic and do not have insulin resistance.

Vaginal bleeding from GLP-1 RAs

There is one published case study of a perimenopausal woman experiencing what appeared to be dulaglutide-related vaginal bleeding⁵.

According to an online clinical trial resource, just 41 people have experienced vaginal bleeding while taking Trulicity (a cousin of semaglutide), 34 from Ozempic, and none reported from Wegovy or Rybelsus.

No vaginal infections were reported to the USA Food and Drug Administration (FDA) in any clinical trials for semaglutide.

Semaglutide and the gut microbiome

The majority of side effects occur in the digestive system (nausea, vomiting, decreased appetite, and abdominal cramping⁶), suggesting a possible drug influence on the gut. We know that semaglutide impacts the gut microbiome, but it’s unclear why these digestive side effects are so common.

But, we’ll discuss exactly how it works a little further down.

While you might expect that the unpleasant digestive symptoms would have a detrimental gut impact, there is evidence that in obesity and type 2 diabetes, the use of semaglutide can positively impact the gut microbiome, overcoming some of the microbial issues with a high-fat diet^7,8.

Research shows that the gut microbiome is implicated in obesity and metabolic disorders, and upon treatment, it is modified⁹.

The abundance and diversity of gut microbiota were considerably decreased with using drugs like semaglutide¹⁰, which is widely considered beneficial in the context of obesity and insulin resistance.

Insulin dysregulation and hormones

We know that insulin directly impacts the ovaries, sending a signal to produce testosterone. In insulin resistance, the increase in insulin can cause a cascade of hormonal signals that result in interruptions to normal menstrual cycles.

The most common insulin resistance-related condition is polycystic ovarian syndrome (PCOS), which is now known to be the result of excess insulin due to resistance. It is less a hormonal condition than a blood sugar dysregulation issue, but the most common features are skipped periods, hard-to-shift weight, and signs of excess androgens like facial hair and acne.

Semaglutide was not thought to affect hormone levels in people using the combined oral contraceptive pill¹¹.

Serious side effects of semaglutide

Serious listed side effects of semaglutide can include thyroid tumours and multiple endocrine neoplasia syndrome type 2, with other side effects including pancreatitis, vision changes, low blood sugar, kidney failure, allergic reaction and gallbladder problems.^3,12

These side effects may provide us with some clues as to how the urinary tract and vagina got mixed up in blood sugar management.

What to do if you’re experiencing urogenital side effects from Wegovy or Ozempic

Talk to your doctor, and report your experiences on Wegovy/Ozempic so they can ensure that the impact is from the drug, not from another cause
Discuss skipping some injections to see if the symptoms subside (though keep in mind it might take longer than a week to shift symptoms, be mindful of any experiments and speak to your doctor)
Explore other options with your doctor
Keep a symptom diary – this can help later when you’re trying to work out if things have gotten better or worse or stayed the same on Wegovy or Ozempic
If semaglutide isn’t a good fit for you, explore non-drug options with a functional medicine doctor, herbalist, nutritionist or naturopath who specialises in metabolic conditions

I want to stay on semiglutide – what can I do for non-severe symptoms?

To treat UTI and urinary tract symptoms, use Aunt Vadge’s Oral UTI Blends
To treat vaginal symptoms, use Aunt Vadge’s BV Herbal Pessary Blend
Life-Space Women’s Microflora Probiotic orally and vaginally as per Killing BV
Download and read Killing BV for treatment tips and tricks
Tools for clearing up a smelly vagina
Talk to an experienced healthcare practitioner about other ways to control blood sugar and weight that can be used in conjunction with Wegovy and Ozempic

How does semaglutide work?

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that mimics the hormone GLP-1. GLP-1 is a hormone produced by the gut wall when we eat, stimulating the pancreas to secrete insulin and thus reducing blood glucose levels.

When you eat, you produce insulin to seek out the glucose absorbed from food and remove it from the blood, where it’s dangerous. You also urinate out some glucose, temporarily increasing urinary glucose levels.

If you have diabetes or insulin resistance, a lot more insulin needs to be released to ‘capture’ all the glucose, taking a bit longer and creating a situation of ‘high blood sugar’ or hyperglycaemia. This increase in blood sugar also increases the urinary output of glucose, typically for longer than in people without insulin resistance.

This is why diabetics are prescribed insulin injections and medications like semaglutide and metformin: to increase insulin levels when they are needed, safely regulating blood sugar levels.

It is not understood how semaglutide impacts the urogenital tract, and there is no research into this. There is, however, research into the impacts of semaglutide on the kidneys and some bacteria, which may offer us some clues.

UNDERSTANDING INSULIN RESISTANCE
If you're a little unclear on how insulin and blood sugar do their important work, our resident insulin resistance expert, Josephine Cabrall, provides a great explanation in our insulin resistance article—with excellent custom-made cartoons!

E. faecalis breaks down GLP-1 (UTIs, AV)

One study¹³ showed that glucagon-like peptide-1 (GLP-1) is utilised by many strains of Enterococcus faecalis, a very common urinary tract pathogen and one of the major players in many cases of aerobic vaginitis (AV).

E. faecalis is a gut microbiome commensal, meaning it belongs in the digestive system, but it does not belong in any meaningful levels in the urinary tract or vagina.

A protease secreted by E. faecalis, GeIE – an established virulence factor – was responsible for inhibiting GLP-1 by cleaving GLP-1 using GeIE. Cleaving by bacteria means splitting up or breaking the bonds between something else, in this case, GLP-1.

These strains can disrupt the epithelial barrier and steal GLP-1 from the digestive system, where it is used for blood sugar management.

But this leaves us with more questions than answers: can E. faecalis do the same in the vagina and urinary tract? Can you even find GLP-1 in the epithelial cells of the vagina or urinary tract? If we increase GLP-1 production using semaglutide, would this subsequently impact E. faecalis numbers?

E. coli increases after GLP-1 RAs (UTIs, AV)

Research demonstrated that upon administration of GLP-1 RAs to mice, a component of Escherichia coli (caseinolytic protease B) and norepinephrine was increased¹⁴, indicating an increase in E. coli populations.

Norepinephrine (noradrenaline) passed into the intestinal lumen, with indirect evidence of sympathetic nervous system activation in the intestinal tract by GLP-1 RA¹⁴.

Under normal conditions, the increase in E. coli did not affect the mice, but in mice with colitis, bacteria were able to pass through the intestine due to normally tight gap junctions being loose¹⁴.

Impacts of GLP-1 RA drugs – what we know

Impacts on kidneys of prolonged GLP-1 RA treatment are largely unknown¹⁵
Increases urinary excretion of sodium, chloride and potassium¹⁵
Increases urinary pH¹⁵
Reduces excretion of magnesium, calcium and phosphate¹⁵
Suggestions of decreased NHE3 activity¹⁵
Increased post-eating (postprandial) blood pressure¹⁵

GLP-1 RA drugs for diabetics

There are several types of GLP-1 RA drugs, all of which are differentiated by their molecular structure and how long they exert their effect. These differences translate to how effective the drug is, tolerance and the potential for side effects.

For example, how big is the molecule, and how long does it last in the human body before it is excreted (half-life)? How similar is the drug to human GLP-1? These all impact how well the drug works for managing blood sugar and weight loss, and common side effects.

GLP-1 is very short-acting with a short half-life¹⁶.

Individual response to semaglutide can’t be predicted – some people love it, some people it simply doesn’t agree with. The drugs worked well in clinical trials to lower blood glucose levels and achieve weight loss.

Kidney input

To understand how and why semaglutide could be contributing to changes in microflora, we have to understand how glucose is managed by the body, and how other factors – like microbes – utilise substances we produce, such as GLP-1.

While insulin release is one way your body deals with incoming glucose, your kidneys also do a lot of heavy lifting.

Without getting into too much detail, the kidneys suck up some of the glucose (renal glucose uptake), then, after a while, spit it back out (reabsorption), when the body has had time to deal with the other glucose using insulin and other mechanisms^17,18.

Your kidneys hold on to glucose, but you’ll urinate some glucose out if they get full. The kidneys of diabetics don’t handle glucose in the same way as those of non-diabetics.

Use of semaglutide for weight loss alone (without type 2 diabetes)

In the USA in particular, many people are using semaglutide as a weight loss tool, which the drug is not specifically approved for, but is a natural effect of managing blood glucose levels adequately. Semaglutide also decreases appetite, another function of our natural human GLP-1 hormone.

This use of semaglutide is what’s known as ‘white label’ use, which is when a drug is known for certain effects, but that’s not the main approved use. Many drugs are safely used this way, under medical supervision.

It is currently unclear which proportion of users reporting urogenital and hormonal side effects have been diagnosed with insulin resistance or type 2 diabetes, and which are using semaglutide as a weight loss tool alone.

References

1.
Ghusn W, De la Rosa A, Sacoto D, et al. Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. JAMA Netw Open. Published online September 19, 2022:e2231982. doi:10.1001/jamanetworkopen.2022.31982
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Keating SK, Wild CEK. Semaglutide and social media: implications for young women with polycystic ovarian syndrome. The Lancet Child & Adolescent Health. Published online May 2023:301-303. doi:10.1016/s2352-4642(23)00033-0
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Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. Published online March 18, 2021:989-1002. doi:10.1056/nejmoa2032183
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Yokoyama H, Nagao A, Watanabe S, Honjo J. Incidence and risk of vaginal candidiasis associated with sodium–glucose cotransporter 2 inhibitors in real‐world practice for women with type 2 diabetes. J of Diabetes Invest. Published online October 19, 2018:439-445. doi:10.1111/jdi.12912
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Vaccaro CJ, Zaidi SMH, Iskander PA, McFadden E. A Case of Dulaglutide-Induced Vaginal Bleed. Cureus. Published online May 9, 2023. doi:10.7759/cureus.38774
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Okeke IG, Camarda AR, Okeke R, Chaughtai S. Semaglutide-induced Hyperemesis Gravidarum. JCEM Case Reports. Published online January 8, 2024. doi:10.1210/jcemcr/luad167
7.
Duan X, Zhang L, Liao Y, et al. Semaglutide alleviates gut microbiota dysbiosis induced by a high-fat diet. European Journal of Pharmacology. Published online April 2024:176440. doi:10.1016/j.ejphar.2024.176440
8.
Kant R, Chandra L, Verma V, et al. Gut microbiota interactions with anti-diabetic medications and pathogenesis of type 2 diabetes mellitus. WJM. Published online July 20, 2022:246-257. doi:10.5662/wjm.v12.i4.246
9.
Tsai CY, Lu HC, Chou YH, et al. Gut Microbial Signatures for Glycemic Responses of GLP-1 Receptor Agonists in Type 2 Diabetic Patients: A Pilot Study. Front Endocrinol. Published online January 10, 2022. doi:10.3389/fendo.2021.814770
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Zhao L, Chen Y, Xia F, et al. A Glucagon-Like Peptide-1 Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota. Front Endocrinol. Published online May 17, 2018. doi:10.3389/fendo.2018.00233
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Jordy AB, Albayaty M, Breitschaft A, et al. Effect of Oral Semaglutide on the Pharmacokinetics of Levonorgestrel and Ethinylestradiol in Healthy Postmenopausal Women and Furosemide and Rosuvastatin in Healthy Subjects. Clin Pharmacokinet. Published online March 30, 2021:1171-1185. doi:10.1007/s40262-020-00976-x
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Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol. Published online July 7, 2021. doi:10.3389/fendo.2021.645563
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LeValley SL, Tomaro-Duchesneau C, Britton RA. Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by Enterococcus faecalis Metalloprotease GelE. Marco ML, ed. mSphere. Published online February 26, 2020. doi:10.1128/msphere.00585-19
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Kato S, Sato T, Fujita H, Kawatani M, Yamada Y. Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms. Sci Rep. Published online April 28, 2021. doi:10.1038/s41598-021-88612-x
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Tonneijck L, Muskiet MHA, Blijdorp CJ, et al. Renal tubular effects of prolonged therapy with the GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes mellitus. American Journal of Physiology-Renal Physiology. Published online February 1, 2019:F231-F240. doi:10.1152/ajprenal.00432.2018
16.
Xu F, Wang KY, Wang N, Li G, Liu D. Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice. Bader M, ed. PLoS ONE. Published online July 27, 2017:e0181939. doi:10.1371/journal.pone.0181939
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Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabetic Medicine. Published online February 2010:136-142. doi:10.1111/j.1464-5491.2009.02894.x
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Rave K, Nosek L, Posner J, Heise T, Roggen K, van Hoogdalem EJ. Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes—results of a hyperglycaemic glucose clamp study. Nephrology Dialysis Transplantation. Published online April 20, 2006:2166-2171. doi:10.1093/ndt/gfl175