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Vaginal microbiota and genitourinary menopausal symptoms: a cross-sectional analysis

Mitchell, Caroline M. MD, MPH1; Srinivasan, Sujatha PhD2; Zhan, Xiang PhD2; Wu, Michael C. PhD2; Reed, Susan D. MD, MPH2,3; Guthrie, Katherine A. PhD2; LaCroix, Andrea Z. PhD4; Fiedler, Tina BS2; Munch, Matthew BS2; Liu, Congzhou MS2; Hoffman, Noah G. MD, PhD5; Blair, Ian A. PhD6; Newton, Katherine PhD7; Freeman, Ellen W. PhD8; Joffe, Hadine MD, MSc9; Cohen, Lee MD10; Fredricks, David N. MD2

doi: 10.1097/GME.0000000000000904
Original Articles

Objective: To examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen.

Methods: For this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial communities were characterized using 16S rRNA PCR and deep sequencing targeting the V3-V4 region. Quantities of Lactobacillus crispatus and Lactobacillus iners were measured using qPCR. Self-reported genitourinary symptoms included: presence and severity of individual symptoms and identification of most bothersome symptom. Glycogen was measured fluorometrically in swab eluate. Serum estradiol (E2) and estrone (E1) were measured by liquid chromatography/mass spectrometry. Associations between bacteria, symptoms, glycogen, and serum estrogens were tested by linear regression or Wilcoxon signed-rank test, adjusted for multiple comparisons. Comparisons between groups used Kruskall-Wallis or Fisher's exact test.

Results: Of the 88 women, 33 (38%) had a majority of Lactobacillus species, whereas 58 (66%) had any Lactobacillus detected. Over half (53%) reported at least one vulvovaginal symptom (most commonly dryness), but symptoms were not associated with the presence of Lactobacillus species. Women with Lactobacillus-dominant communities had higher unconjugated serum estrone, but no difference in vaginal glycogen levels, compared with those with non-Lactobacillus-dominant communities. Higher serum E2 and E1 were not associated with either higher vaginal glycogen or detection of individual genera.

Conclusions: Presence of Lactobacillus-dominant vaginal microbiota was not associated with fewer vulvovaginal symptoms. Serum estrone was higher in women with Lactobacillus dominance, but vaginal-free glycogen was not associated with composition of the vaginal microbiota.

1Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA

2Fred Hutchinson Cancer Research Center, Seattle, WA

3Department of Obstetrics & Gynecology, University of Washington, Seattle, WA

4Department of Family Medicine and Public Health, University of California at San Diego, La Jolla, CA

5Department of Laboratory Medicine, University of Washington, Seattle, WA

6Department of Pharmacology, University of Pennsylvania, Philadelphia, PA

7Group Health Research Institute, Seattle, WA

8Department of Obstetrics & Gynecology and Psychiatry, University of Pennsylvania, Philadelphia, PA

9Brigham and Women's Hospital and Dana Farber Cancer Center, Boston, MA

10Department of Psychiatry, Massachusetts General Hospital, Boston, MA.

Address correspondence to: Caroline M. Mitchell, MD, MPH, Vincent Center for Reproductive Biology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. E-mail:

Received 13 February, 2017

Revised 15 March, 2017

Accepted 15 March, 2017

These data were presented in part at the annual meeting of the Infectious Disease Society of Obstetrics & Gynecology, August 11-13, 2016.

Funding/support: This project was funded by the National Institutes of Health as a cooperative agreement issued by the National Institute of Aging: #U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700.

Financial disclosure/conflicts of interest: Dr Mitchell serves as a consultant for Perrigo Pharmaceuticals and Symbiomix Therapeutics. Dr Mitchell is also supported by a Clinical Scientist Development Award from the Doris Duke Foundation. Dr Reed has received grant funding from Bayer. Dr Joffe is a consultant for Merck & Co, Inc, NeRRe Therapeutics, Mitsubishi Tanabe Pharma America Inc, SAGE Therapeutics. Dr Joffe has also received grant funding from Merck & Co, Inc. Dr Cohen has received research funding from Cephalon, Inc, JayMac Pharmaceuticals, Takeda/Lundbeck Pharmaceuticals.

© 2017 by The North American Menopause Society.