Vaginal microbiota in menopause - UI Scholars Hub

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Journal of General - Procedural Dermatology & Venereology Journal of General - Procedural Dermatology & Venereology Indonesia

Indonesia

Volume 1

Number 3 December Article 2

12-31-2016

Vaginal microbiota in menopause Vaginal microbiota in menopause

Martinus Martinus

Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital

Larisa Paramitha Wibawa

Evita Halim Effendi

Shannaz Nadia Yusharyahya

Hanny Nilasari

See next page for additional authors

Follow this and additional works at: https://scholarhub.ui.ac.id/jdvi

Part of the Dermatology Commons, Integumentary System Commons, and the Skin and Connective Tissue Diseases Commons

Recommended Citation Recommended Citation

Martinus, Martinus; Wibawa, Larisa Paramitha; Effendi, Evita Halim; Yusharyahya, Shannaz Nadia; Nilasari, Hanny; and Indriatmi, Wresti (2016) "Vaginal microbiota in menopause," Journal of General - Procedural Dermatology & Venereology Indonesia: Vol. 1: No. 3, Article 2.

DOI: 10.19100/jdvi.v1i3.27

Available at: https://scholarhub.ui.ac.id/jdvi/vol1/iss3/2

This Article is brought to you for free and open access by UI Scholars Hub. It has been accepted for inclusion in Journal of General - Procedural Dermatology & Venereology Indonesia by an authorized editor of UI Scholars Hub.

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Vaginal microbiota in menopause Vaginal microbiota in menopause

Authors Authors

Martinus Martinus, Larisa Paramitha Wibawa, Evita Halim Effendi, Shannaz Nadia Yusharyahya, Hanny Nilasari, and Wresti Indriatmi

This article is available in Journal of General - Procedural Dermatology & Venereology Indonesia:

https://scholarhub.ui.ac.id/jdvi/vol1/iss3/2

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J Gen Pro DVI. 2016;1(3):86-92 86 Review article

Vaginal microbiota on menopause

Martinus, Larisa Paramitha Wibawa, Evita Halim Effendi, Shannaz Nadia Yusharyahya, Hanny Nilasari, Wresti Indriatmi

Email: martinustarina86@gmail.com

Abstract

The human vagina together with its resident, microbiota, comprise a dynamic ecosystem. Normal microbiota is dominated by Lactobacillus species, and pathogen microbiota such as Gardnerella species and Bacteroides species can occur due to decrease in Lactobacillus domination. Lactobacillus plays an essential role in keeping normal vaginal microbiota in balance. Vaginal microbiota adapts to pH change and hormonal value. Changes in the vaginal microbiota over a woman’s lifespan will influence the colonization of pathogenic microbes. They include changes in child, puberty, reproductive state, menopause, and postmenopause. Estrogen levels change will affect the colonization of pathogenic microbium, leading to genitourinary syndrome of menopause.

Vulvovaginal atrophy is often found in postmenopausal women, and dominated by L. iners, Anaerococcus sp, Peptoniphilus sp, Prevotella sp, and Streptococcus sp. The normal vaginal microbiota’s imbalance in menopause will cause diseases such as bacterial vaginosis, and recurrent vulvovaginal candidiasis due to hormonal therapies. Changes in the vaginal microbiota due to bacterial vaginosis are characterized by decrease in H2O2-producing Lactobacillus. They are also caused by the increase in numbers and concentration of Gardnerella vaginalis, Mycoplasma hominis, and other anaerob species such as Peptostreptococci, Prevotella spp, and Mobiluncus spp.

Keywords: vagina, microbiota, menopause, Lactobacillus, bacterial vaginosis

Abstrak

Vagina dengan mikrobiota di dalamnya membentuk ekosistem yang dinamis. Mikrobiota normal didominasi oleh spesies Lactobacillus, dan mikrobiota patogen seperti spesies Gardnerella dan spesies Bacteroides dapat timbul sebagai akibat berkurangnya dominasi Lactobacillus. Lactobacillus berperan penting dalam menjaga keseimbangan mikrobiota vagina normal. Mikrobiota pada vagina beradaptasi terhadap perubahan pH dan kadar hormon. Perubahan siklus hidup wanita akan memengaruhi keseimbangan mikrobiota normal di vagina.

Perubahan tersebut meliputi perubahan pada anak-anak, pubertas, masa reproduksi, menopause, dan pascamenopause. Perubahan pada estrogen akan memengaruhi kolonisasi mikroba patogen, mengakibatkan genitourinary syndrome pada menopause. Atrofi vulvovagina sering ditemukan pada wanita pasca menopause, cenderung didominasi oleh L. iners, Anaerococcus sp, Peptoniphilus sp, Prevotella sp, dan Streptococcus sp.

Ketidakseimbangan mikrobiota normal vagina pada menopause menyebabkan berbagai penyakit, yaitu vaginosis bakterialis, dan kandidiasis vulvovaginalis pada terapi sulih hormon. Perubahan mikrobiota vagina pada vaginosis bakterialis ditandai dengan penurunan Lactobacillus penghasil H2O2 dan peningkatan jumlah dan konsentrasi Gardnerella vaginalis, M. hominis, dan beberapa spesies anaerob lain yaitu Peptostreptococci, Prevotella spp, dan Mobiluncus spp.

Kata kunci: vagina, mikrobiota, menopause, Lactobacillus, vaginosis bakterialis

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J Gen Pro DVI. 2016;1(3):86-92 87

Introduction

Microbiota is a community of microorganism - both commensal and pathogenic - which resides in the human body. Microbiota can be found in organs such as the skin, oral cavity, intestines, and vagina.

Although microbiota is also often referred to as microflora, the term microbiota is deemed more suitable; as biota refers to a group of organism in a certain ecosystem, while flora indicates plants.¹ The microbiota in human vagina forms a dynamic ecosystem. In the past 20 years, biochemical and culture methods have been implemented in order to examine the composition of microbiota in a normal vagina, and also to categorise normal and pathogenic microbiota. Nugent score examines normal microbiota -dominated by Lactobacillus, and increase of pathogenic microbiota, i.e. Gardnerella and Bacteroides as a result of the decrease in Lactobacillus domination.²

Zhou et al. found several types of Lactobacillus inside human vagina. The study also found that Lactobacillus’s role in producing lactic acid can be replaced by anaerobic bacteria.³Another research conducted by Hyman et al. also showed that organisms which were previously thought to be pathogenic (Gardnerella vaginalis, Peptostreptococcus, Prevotella, and Streptococcus), were often found in healthy women.⁴

This paper describes vaginal microbiota milieu on menopausal woman and diseases caused by microbiota changes.

Menopause

Definition

Menopause is physiologic on women, which is marked by the stopping of menstrual cycle and the loss of function of ovarian follicles. Normal and spontaneous menopause is defined as 12 months after menstrual cycle has stopped. Natural menopause occurs on the average age of 52 years old.⁵

Early menopause occurs on women age of 40-45 years old, and is experienced by approximately 5%

of women around the world. Premature menopause occurs before the age of 40, and is usually caused by the removal of both ovaries through surgery.

Induced menopause occurs after oophorectomy or ablation of ovarian function (attributable to chemotherapy or radiation on pelvis). The number

of post-menopause women is estimated to have increased to 1,1 billion in 2025.⁵Slight hormonal change usually occurs on women in their third decade.⁶

Physiology

During perimenopause (transition) phase, there is a change in the menstrual cycle and endocrine system, resulting in ovaries losing sensitivity to gonadotropin stimulation, which directly affects ovarian follicle functions.^7,8

Under condition of no organ abnormality caused by follicle-stimulating hormone (FSH), shorter menstrual cycle (< 25 days) is the most common change occurring during perimenopause. This results in decreasing of oocytes number being produced and shortening of follicular phase.

However, when ovulation occurs, the luteal phase still lasts in 14 days.⁹

Clinical Symptoms

Perimenopause is marked by variation in hormonal level in the blood. Common symptoms include hot flashes, insomnia, weight gain, mood changes, irregular menstruation, breast pain (mastodinia), depression, and headache.^5,7,8,10

Clinical symptoms of perimenopause vary from six years before until several years after the last menstruation. The loss of vaginal rugae causes vagina wall to flatten, resulting in woman feeling discomfort during sexual intercourse. The risk to have endometriosis and adenomyosis is increased in women who undergo hormone replacement therapy.^7,8

Microbiota

During a woman’s life cycle, vaginal microbiota changes hourly or daily. The ecosystem is known to be affected by the host’s race as well as internal and external factors.^3,11 Internal factors include hormonal changes which mark the stage of women life: puberty, menstrual cycle, pregnancy, and menopause.⁸External factors include contraception method, sexual behaviour (age of the first sexual intercourse, frequency of sexual intercourse, number of sexual partners), and sexually transmitted infection history. Moreover, to some extent, it is also influenced by diet and the use of topical hygiene products and medication.¹¹

Normal microbiota during menopause and postmenopause

Menopause starts when the number of primordial follical decreases to a very low level. Primordial

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J Gen Pro DVI. 2016;1(3):86-92 88 Table 1. Change of vaginal structure and function due to the decrease of estrogen level on menopause

Change References

Structure

Thinning of vaginal epithelial cells

- Loss of rugae Farage et al. (2006)¹³

- Pale, petechiae Pandit et al. (1997)¹⁴

- Atrophy Maloney et al. (2001)¹⁵

Dermis - Fusion of collagen tissues and hyalinisation

Pandit et al. (1997)¹⁴

- Fragmentation of elastin tissue Pandit et al. 1997)¹⁴ Vascular system - Progressive avascularisation Long et al. (2006)¹⁶ Function

Dispareunia Robinson et al. (2003)¹⁷

Loss of elasticity Long et al. (2006)¹⁶

Dryness Robinson et al. (2003)¹⁷

Decrease in blood flow Tsai et al. (1987)¹⁸

follicles gradually decrease in number since birth.

Estrogen level in plasma decreases from 129 ng/L during reproductive period to 18 ng/L after menopause.¹²Due to the decrease in the estrogen level, change will occur in vaginal structure and function, as described in table 1.^13-18

Microbiota on vagina adapt to the change of Vagina’s pH and hormonal level. On perimenopause, the decrease in number of vaginal lactobacillus lowers its role in protecting the vagina against colonisation of other bacteria. As a result, there are more commensal species living in vagina when compared to reproduction period.¹⁹

Vaginas in postmenopausal phase often have colonisation of pathogenic organism. The change of vaginal pH from acidic (pH 3.8-4.5) to base results in domination of pathogenic bacteria in vagina.

Organisms which can be isolated from postmenopause women’s vagina using culture method are G. vaginalis (27%), U. urealyticum (13%), Prevotella (33%) and Coliform (41%).

Bacteroides (40%) and E. coli (35%) also can be found in postmenopausal women who did not

undergo hormone replacement therapy.⁸ On postmenopausal women, colonisation of E. coli in the vagina is inversely proportionate to Lactobacillus; rapid growth of Lactobacillus is related to low E. coli colonisation.²⁰Researches on vaginal microbiota on postmenopausal women can be seen on table 2.

Vulvovaginal atrophy, commonly found in postmenopausal women, tend to be dominated by L. iners, Anaerococcus sp., Peptoniphilus sp., Prevotella sp., and Streptococcus sp.²¹

Estrogen therapy (hormone replacement) is effective to increase the number of Lactobacillus spp in vulvovaginal atrophy. However, there is no known effect of the increase in Lactobacillus to the improvement of vulvovaginal atrophy symptoms.²² Brotman et al. classify vaginal microbiota community on 87 women of age 35-60 years old using gene 6S ribosomal RNA analysis, comparing composition of vaginal microbiota with menopause transition stage (premenopause, perimenopause, and postmenopause), signs of vulvovaginal atrophy and age. The comparison can be seen on table 3.²³

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J Gen Pro DVI. 2016;1(3):86-92 89 Table 2. Researches on vaginal microbiota on postmenopausal women*

Research population Menopause parameter

Research parameter

Result Reference

50 postmenopausal women aged 55-73 (x̄

= 63,7), 14 underwent hormone replacement therapy

Not specified Culture No significant difference

Osborne et al.

(1979)

28 healthy women (x̄

= 59 years old)

> 2 years since last menstruation

Culture 29% sterile culture 19% containing anaerobes

Blum et al. (1981)

46 postmenopausal women

None Culture 65% Lactobacillus

positive

Larsen et al.

(1982) 171 healthy women

aged 16-65 on cancer prevention program

None Culture Increase of G.

vaginalis

Ceddia et al.

(1989)

350 postmenopausal patients with urinary tract infections, aged 65-84 (x̄ = 72,3), > 3 months since

hormone replacement therapy

Old age Culture 20% Lactobacillus dominance

Milsom et al.

(1993)

73 healthy postmenopausal women, no hormone replacement therapy in ≥ 1 year.

≥ 5 years since last menstruation, FSH level

Culture, Gram staining/ lactic acid production using Nugent criteria,

production of H2O2

13% Lactobacillus dominance 87% intermediate 49% Lactobacillus positive

Hillier et al. (1997)

100 healthy postmenopausal women

FSH level Gram staining/

modified Nugent score

44% normal flora 17% intermediate 18% bacterial vaginosis 21% null flora

Taylor-Robinson et al. (2002)

20 healthy postmenopausal women aged 44-72 (x̄

= 58,9)

Not specified Culture, Gram staining/

Nugent score, PCR/ DGGE

95% Lactobacillus positive

30% normal 30% intermediate 40% bacterial vaginosis

Burton et al.

(2002)

*Adapted from reference no. 2 FSH: Follicle-stimulating hormone PCR: Polymerase chain reaction

DGGE: Denaturing gradient gel electrophoresis

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J Gen Pro DVI. 2016;1(3):86-92 90 Table 3. Demographic status and clinical data, based on menopause transition status*

Data and clinical symptoms Premenopause (%)

Perimenopause (%)

Postmenopause (%)

P (Fischer exact P

value) CST

(Community state types)

CST I 14 (46,7) 6 (20,7) 7 (25,0) 0,004

CST II 1 (3,3) 6 (20,7) 1 (3,6)

CST III 10 (33,3) 11 (37,9) 5 (17,9)

CST IV-A 0 (0) 2 (6,9) 8 (28,6)

CST IV-B 5 (16,7) 3 (10,3) 5 (17,9)

CST V 0 (0) 1 (3,5) 2 (7,1)

Sign of vulvovaginal atrophy

None 27 (93,1) 21 (87,5) 12 (46,2) 0,000

Light 2 (6,9) 2 (8,3) 9 (34,6)

Medium 0 (0) 1 (4,2) 5 (19,2)

Sign of vagina dryness

None 28 (96,6) 23 (92,0) 17 (60,7) 0,003

Light 1 (3,5) 2 (8,0) 5 (17,9)

Medium 0 (0) 0 (0) 5 (17,9)

Severe 0 (0) 0 (0) 1 (3,6)

Age 35-39 years 4 (13,3) 1 (3,5) 1 (3,6) 0,000

40-44 years 9 (30,0) 5 (17,2) 0 (0)

45-49 years 13 (43,3) 12 (41,4) 1 (3,6)

50-54 years 4 (13,3) 10 (34,5) 8 (28,6)

55-60 years 0 (0) 1 (3,5) 18 (64,3)

*Adapted from reference no. 2

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J Gen Pro DVI. 2016;1(3):86-92 91 The term atrophy seems to be inadequate in

explaining the various menopause symptoms which are related to the physical change in vulva, vagina, and lower urinary tract due to estrogen deficiency.

Vulvovaginal atrophy describes condition of postmenopausal vulvovagina without related clinical symptoms. Moreover, Portman and Gass suggest that the word atrophy has negative connotation in women, and vagina is not a word generally used in daily life. Therefore, the term genitourinary syndrome of menopause is deemed more appropriate.²⁴

Bacterial vaginosis on menopause

Signs of bacterial vaginosis include nonpurulent, homogenous, and putrid vaginal secretion, increase of pH in vagina to >4,5 and clue cells on microscopic examination in vaginal secretion.

Change in vaginal microbiota on bacterial vaginosis is marked by the decrease in number of H2O2-

producing Lactobacillus and the increase in number and concentration of Gardnerella vaginalis, M.

hominis, as well as several other anaerobe species such as Peptostreptococci, Prevotella spp, and Mobiluncus spp.²⁵

Cauci et al. conducted a research on bacterial vaginosis prevalence on perimenopausal and postmenopausal women in Italy. The research population was 1486 Caucasian Italian women age 40-79, classified as fertile (regular menstruation cycle), perimenopause (irregular menstruation cycle), and post menopause with and without hormone replacement therapy. The result showed no significant difference in bacterial vaginosis prevalence in fertile women and perimenopausal women. However, on postmenopausal women there was a lower prevalence of bacterial vaginosis.²⁶ In a study conducted by Hoffman et al. on 1016 women age 57-85 years old on the prevalence of bacterial vaginosis on postmenopausal women in the United States, the prevalence of bacterial vaginosis was 23%, and increased to 38% in the five years follow-up.²⁷

Conclusion

Lactobacillus has a significant role in maintaining the balance of microbiota in normal vagina. Several changes occurring in women life cycle affects the balance of vaginal microbiota. Change of estrogen level on menopause causes several vaginal infection and vulvovaginal atrophy which may cause discomfort. It is important to give education on

general menopause condition and their medication in order to improve the quality of life of the patients.

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