The Genitourinary syndrome of menopause (GSM)—formerly known as vulvovaginal atrophy and atrophic vaginitis—refers to a constellation of physical changes in the vulva, vagina, and lower urinary tract, and the associated sexual and urinary tract symptoms that result from a lack of estrogen in these tissues. Symptoms may include pain during penetrative sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does not resolve without ongoing treatment. Complications may include urinary tract infections. Diagnosis is typically based on symptoms.
The former term atrophic vaginitis is now regarded as inaccurate, as it suggests that the vagina is inflamed or infected. Inflammation and infection are not the major components of postmenopausal changes to the vagina. Similarly, the former term "vulvovaginal atrophy" does not reflect the related changes of the labia, clitoris, vestibule, urethra and bladder. The neglected negative effects on the lower urinary tract can be the most troubling symptoms of menopause for women. "Genitourinary syndrome of menopause" was therefore determined to be more accurate than the former terms by two professional societies. It is an umbrella term for vulvovaginal atrophy, atrophic vaginitis, urogenital atrophy and vaginal atrophy that occurs due to a decrease in estrogen.
The decrease in estrogen typically occurs following menopause. Other causes may include breastfeeding, surgical removal of ovaries, or specific medications. Risk factors include smoking.
First line treatment for the genitourinary syndrome of menopause is topical estrogen. There is ongoing research on other forms of hormone replacement therapy.
Risk factors In a majority of postmenopausal women, there are risk factors that can contribute to atrophic vaginitis. Specifically, these risk factors are directly related to decreased estrogen levels and vaginal health. Some risk factors include
Bilateral Oophorectomy: Women who undergo surgical removal of both ovaries, potentially causing a decline in estrogen levels. Primary Ovarian Insufficiency: Ovaries fail to properly function before 40 years of age, causing a decrease in estrogen levels. Ovarian Failure due to Radiation or Arterial Embolization: These treatments involve radiation or embolization of the ovaries and can cause ovarian damage. This leads to decreased estrogen production and symptoms of atrophic vaginitis. Hypothalamic-Pituitary Disorders: These disorders directly affect the hypothalamus or pituitary gland, disrupting hormone production. Anti-Estrogen Medications: Medications such as Danazol or Leuprolide can lower estrogen levels. Postpartum Breastfeeding: Breastfeeding can cause lower estrogen levels due to hormonal changes. Breast Cancer Survivors: Chemotherapy, selective estrogen receptor modulators (e.g. Tamoxifen and Raloxifene), or aromatase inhibitors (e.g. Letrozole, Anastrozole, and Exemestane) can lead to decreased estrogen levels and therefore side effects that include atrophic vaginitis. Cigarette smoking
All of these factors impact estrogen levels and vaginal health, causing an increase in Atrophic vaginitis development.
Causes GSM may be caused by tissue thinning, loss of elasticity, and loss of vaginal fluids from low estrogen levels. Normally, estrogen helps the vagina shed old cells, which are then converted into lactic acid by good bacteria. This keeps the vagina's pH acidic and healthy. When estrogen levels drop, this process slows down, leading to thinner vaginal tissue, less moisture, and a less acidic environment. As a result, there's a higher risk of vaginal and urinary tract infections from bacteria that would normally be deterred by a healthy environment. The drop in estrogen may be caused by normal menopause or by treatments such as chemotherapy or certain medications.
Those with or had a history of breast cancer may be at a higher risk of developing GSM due to chemotherapy and other hormone-blocking treatments. Estrogen is crucial for women's sexual and urinary health. It supports the tissues in the lower vagina and urinary tracts to keep them thick, elastic, and moist and ensuring good blood flow. Estrogen helps maintain a thick, glycogen-rich vaginal lining, which healthy bacteria use to produce lactic acid to keep the vaginal environment acidic, reducing infection risks. In premenopausal women, the main form of estrogen is called estradiol and fluctuates between 40 and 200 pg/mL, rising to 600 pg/mL during ovulation. Postmenopause, estrogen levels drop significantly to 5-18 pg/mL, leading to gradual changes in the urogenital area. All tissue types such as connective, epithelial, muscular, blood vessels, and nerves are affected and become thinner and less effective, which increases risk of infections, inflammation, injuries, and sores. Blood flow and sensation can decrease, causing pain during sex. pH level can become unbalanced due to decreased lactic acid production, which can allow harmful bacteria and fungi to grow and cause infections.
Antiestrogen medications may also contribute to the development of atrophic vaginitis. These medications include danazol, nafarelin, and medroxyprogesterone. Additional risk factors include smokers, those who have not given birth naturally (through the vagina), and increased prolactin levels while lactation.
Signs and symptoms
After menopause, the vaginal epithelium changes and becomes a few layers thick. Many of the signs and symptoms that accompany menopause also occur in GSM, sometimes making diagnosis difficult. The earliest symptoms of GSM may be decreased vaginal lubrication, while other symptoms may appear later. Genitourinary symptoms include dryness pain itching burning soreness pressure white discharge malodorous discharge due to infection painful sexual intercourse bleeding after intercourse painful urination blood in the urine increased urinary frequency incontinence increased susceptibility to infections decreased vaginal lubrication urinary tract infections painful urination difficulty sitting difficulty wiping thin, clear discharge
Diagnosis It can be challenging to diagnose atrophic vaginitis given that the symptoms are nonspecific for many postmenopausal women. Since women can have signs and symptoms that could be attributed to other causes, diagnosis is based upon the symptoms that cannot be better accounted for by another diagnosis.
Differential Diagnosis To determine if atrophic vaginitis is the cause for a patient's symptoms, clinical history, physical exam, and some laboratory tests may be used. Other diagnosis that need to be ruled out include bacterial vaginosis, trichomoniasis, candidiasis, and contact irritation from irritants such as soaps, pantyliners, or tight-fitting clothing.
Clinical Examination Few lab tests prove this diagnosis, so a visual exam is useful. The observations of the following may indicate lower estrogen levels: little pubic hair, loss of the labial fat pad, thinning and resorption of the labia minora, and the narrowing of the vaginal opening. An internal exam will reveal the presence of low vaginal muscle tone, and the lining of the vagina can appear smooth, shiny, and pale with loss of folds. The cervical fornices may disappear and the cervix can appear flush with the top of the vagina. Inflammation is apparent when the vaginal lining bleeds easily and appears swollen.
Lab Examination The vaginal pH will become less acidic and be at around 4.5 or higher. This is typically taken by placing Litmus test strip on the wall of the vagina. There are also changes to cellular structures under the microscope including reduced vascularization (blood supply), atrophy of epithelial tissue leading to reduced thickness, and paleness. Microscopy laboratory tests may be used to rule out symptoms caused by trichomoniasis and other bacteria. A Papanicolaou test, also known as a pap test, would not be useful as it does not correlate strongly with the symptoms of atrophic vaginitis.
Vaginal Maturation Index (VMI) The Vaginal Maturation Index (VMI) is a measure used to assess the composition of different types of cells in the vaginal lining. It helps to evaluate the hormonal environment in the vagina by calculating the proportion of different types of cells present in the vagina. During different life stages, such as before the first menstural cycle, during reproductive years, and after menopause, the distribution of these cell types changes. VMI is determined using a specific formula and provides a more comprehensive view of the hormonal effects on the vagina over time than a single hormone level measurement. VMI is particularly useful in clinical research for evaluating the impact of hormone therapy and changes in sexual function during menopause. VMI is also a better measure of vaginal atrophy than patient-reported symptoms of vaginal dryness.
Treatment Symptoms of genitourinary syndrome of menopause (GSM) do not resolve without treatment. Severity and prevalence of symptoms vary, so treatment is tailored to each individual. Vaginal estrogen therapy is the first-line treatment, and is safe for most patients. While not widely prescribed previously due to concern for hormonal implication in cancer, the black box on estrogen has been lifted due to many studies proving that vaginal estrogen has a reassuring safety profile and is overwhelmingly free from serious side effects. Patients with history of hormone-sensitive breast cancer or endometrial cancer should have a shared-decision making conversation with their physician. If other health problems are also present, these can be taken into account when determining the best course of treatment. For those who have symptoms related to sexual activities, a lubricant may help alleviate symptoms. Some people can have symptoms that are widespread and may be at risk for osteoporosis. Recent research showed a medication called ospemifene can be an alternative oral treatment if vaginal products or hormone therapy is not suitable for patients surviving gynecological cancer. Ospemifene can increase collagen production to improve vaginal tissue, which will help reduce GSM symptoms. Studies have shown this medication has helped increase vaginal pH, elasticity, and moisture to improve vaginal health as well as sexual and emotional well-being.
Topical treatment with estrogen is effective when the symptoms are severe and relieves the disruption in pH to restore the microbiome of the vagina. When symptoms include those related to the urinary system, other treatments can be prescribed by a physician. Like any medication, use of estrogen for treatment does come at some risk, but most patients are able to use local hormone cream without complication. Those who are treated with estrogen may be at a higher risk of developing vaginal candidiasis since estrogen allows lactobacilli to increase in levels. Additionally, it is recommended that soaps and other irritants are avoided.
Some treatments have been developed more recently. These include selective estrogen receptor modulators, vaginal dehydroepiandrosterone, and laser therapy.