Microbiome and Polycystic Ovaries

NCT ID: NCT04836910

Last Updated: 2024-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-09-01

Study Completion Date

2027-03-30

Brief Summary

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Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder among women in reproductive age with an estimated prevalence of 5% to 19.5%. It is a chronic complex syndrome with psychological (depression and anxiety), reproductive and metabolic abnormalities. The etiology seems to be multifactorial. Lately, interest regarding the association between PCOS women and gut macrobiotic have been emerged. Hyperandrogenism was correlated with those changes in the microbiota which reflects the fact that the microbiome can influence the development and pathology of PCOS .

Therefore, aim of this study is to explore the diversity and alternations of the vaginal and the gut microbiome in patients with PCOS during common therapeutic interventions and connect them to different phenotypes of the syndrome.

Detailed Description

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Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder among women in reproductive age with an estimated prevalence of 5% to 19.5%. It is a chronic complex syndrome with psychological (depression and anxiety), reproductive and metabolic abnormalities. The etiology seems to be multifactorial. It seems there are both genetic, epigenetic and environmental contributors (almost 100 susceptible genes were identified).

The quality of life (QQL) of women suffering from PCOS is significantly reduced in all domains (functional ability, physical and emotional) and major health problems is correlated to PCOS. Women with PCOS demonstrate hyperinsulinemia and insulin resistance. They have an increased risk for type 2 diabetes and impaired glucose tolerance. Studies have shown that adipocyte function is considerably aberrant in women with PCOS including: lower lipase activity, defective glucose transport and dyslipidemia. Obesity is more prevalent in women with PCOS. They are also exposed to long term risk for additional disorders like cardiovascular diseases (atherosclerosis) or even cancer (endometrial or ovarian) .

PCOS is the primary cause of anovulatory subfertility. Furthermore, women with PCOS are at risk for pregnancy and obstetrical complications including preterm birth, pre- eclampsia and meconium aspiration syndrome of neonates after birth.

PCOS is diagnosed according the Rotterdam criteria . It requires 2 out of 3 symptoms: 1. Hyperandrogenism or excess levels of androgen)- clinical and/ or biochemical (presence of hirsutism, acne or alopecia). 2. Oligo or anovulation (including menstrual dysfunction). 3. PCO-M polycystic ovaries morphology (over 12 follicles, 2-9 mm or increased ovarian volume).

The term microbiome describes the genetic material of all the microbes (bacteria, fungi, protozoa and viruses) that live onside and inside the human body. It is important for development of the body, immunity and nutrition. The microbiome may influence the susceptibility to different infectious diseases and contribute to chronic illnesses.

The gut microbiota contains 100 trillion microbes. When discussing gut bacteria, it is primarily referred to the large intestine (colon). Lately, interest regarding the association between PCOS women and gut macrobiotic have been emerged. Hyperandrogenism was correlated with those changes in the microbiota which reflects the fact that the microbiome can influence the development and pathology of PCOS . Preliminary studies have shown that different bacterial species colonize the gut of PCOS induced animals compared to controls.

A novel theory was developed concerning the development of PCOS. A diet high of sugars sets as a convenient platform for gram negative bacteria ("bad" bacteria) while reducing "good" bacteria. The cell wall of the gram negative bacteria is comprised of lipopolysaccharide (LPS) which stimulates the immune system. The high sugar diet increases the permeability of the gut ("leaky gut") leading to chronic inflammation which produces impaired insulin receptor function. The insulin facilitates an increase in the production of androgens by the ovaries which leads to PCOS .

The dysbiosis was correlated with sex hormone levels and ovarian changes. In addition, treating PCOS using lactobacillus ("good" bacteria) transplantation showed improved ovarian functions.

Even though, several studies established the connection between the dysbiosis of the gut and PCOS, only a few studies were conducted on the association between the vaginal microbiome and the development of PCOS. To detail, the vaginal microbiome in PCOS is more diverse and heterogeneous, with the relative abundance of certain species (such as Mycoplasma) and lower level of others (such as Lactobacillus which keeps the vagina acidic) .

Moreover, should this association be strengthen between the microbiome of the gut and vagina to PCOS, it could serve as grounds to new horizons for treatment. There are several therapies for PCOS treatment (Life style interventions, improving metabolic dysfunction and medical treatment ), however, currently, there is no ideal therapy that fully treats all the clinical features.

Due to all the aforementioned, we aim of this study is to explore the diversity and alternations of the vaginal and the gut microbiome in patients with PCOS during common therapeutic interventions and connect them to different phenotypes of the syndrome.

Study design A prospective longitudinal case control study that will be conducted at Sheba Medical Center (tertiary medical center).

Study group will include 20 women in fertility age (age 18-42) diagnosed with PCOS according to the Rotterdam Criteria who haven't started any kind of treatment. The control group would be healthy women matched by age. Women in both groups will be recruited at the Endocrine outpatient's clinics. All women will sign informed consent form after receiving information on the study from one of the research team members.

Vaginal and rectal samples will be collected during the regular clinic visits that will be set by the medical interventions requirements (including: dietary recommendations, physical activity, hormonal contraception, insulin resistance treatment, fertility treatment, pregnancy follow-up):

1. at first visit after recruitment
2. 1 month following first intervention
3. 3 month following first intervention

Conditions

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Polycystic Ovary Syndrome Microbial Colonization

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Study Group: Women with Polycystic Ovary Syndrome

Woen diagnosed with Polycystic Ovary Syndrome according to the Rotterdam Criteria (requires 2 out of 3 symptoms: 1. Hyperandrogenism or excess levels of androgen. 2. Oligo or anovulation. 3. Polycystic ovaries on ultrasound - over 12 follicles, 2-9 mm or increased ovarian volume),who haven't started any treatment

Dietary recommendations

Intervention Type OTHER

Fruit, vegetables, legumes (e.g. lentils and beans), nuts and whole grains (e.g. unprocessed maize, millet, oats, wheat and brown rice).

At least 400 g (i.e. five portions) of fruit and vegetables per day excluding potatoes, sweet potatoes, cassava and other starchy roots.

Less than 10% of total energy intake from free sugars Less than 30% of total energy intake from fats. Unsaturated fats (found in fish, avocado and nuts, and in sunflower, soybean, canola and olive oils) are preferable to saturated fats.

Less than 5 g of salt (equivalent to about one teaspoon) per day.

Oral contraceptive pills

Intervention Type DRUG

Hormonal treatment

Metformin

Intervention Type DRUG

Insulin resistance treatment

Cohort Group: Women without Polycystic Ovary Syndrome

No interventions assigned to this group

Interventions

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Dietary recommendations

Fruit, vegetables, legumes (e.g. lentils and beans), nuts and whole grains (e.g. unprocessed maize, millet, oats, wheat and brown rice).

At least 400 g (i.e. five portions) of fruit and vegetables per day excluding potatoes, sweet potatoes, cassava and other starchy roots.

Less than 10% of total energy intake from free sugars Less than 30% of total energy intake from fats. Unsaturated fats (found in fish, avocado and nuts, and in sunflower, soybean, canola and olive oils) are preferable to saturated fats.

Less than 5 g of salt (equivalent to about one teaspoon) per day.

Intervention Type OTHER

Oral contraceptive pills

Hormonal treatment

Intervention Type DRUG

Metformin

Insulin resistance treatment

Intervention Type DRUG

Other Intervention Names

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World Health Organisation (WHO) recommendations

Eligibility Criteria

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Inclusion Criteria

Study group: Untreated women diagnosed with PCOS that are planned for intervention.

Control group: Women without PCOS visiting the gynecologic outpatient's clinics.

Exclusion Criteria

1. Endocrine abnormality ( Cushing's syndrome, congenital adrenal hyperplasia, thyroid disorder, hyperprolactinemia and androgen-secreting tumor).
2. Premature ovarian failure 2. Active malignancy 3. Participants taking antibiotics/ probiotics, hormonal, vaginal or laxative medicine (in the previous week).

4\. Vaginitis/ Pelvic Inflammatory Disease (PID)
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Dr. Aya Mohr-Sasson

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Sheba Medical Center

Ramat Gan, , Israel

Site Status

Countries

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Israel

Central Contacts

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Aya Mohr-Sasson, M.D

Role: CONTACT

0523692906

Facility Contacts

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Aya Sasson

Role: primary

0523692906

References

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American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. Obstet Gynecol. 2018 Jun;131(6):e157-e171. doi: 10.1097/AOG.0000000000002656.

Reference Type BACKGROUND
PMID: 29794677 (View on PubMed)

Macut D, Bjekic-Macut J, Rahelic D, Doknic M. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract. 2017 Aug;130:163-170. doi: 10.1016/j.diabres.2017.06.011. Epub 2017 Jun 12.

Reference Type BACKGROUND
PMID: 28646699 (View on PubMed)

Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016 Jul;106(1):6-15. doi: 10.1016/j.fertnstert.2016.05.003. Epub 2016 May 24.

Reference Type BACKGROUND
PMID: 27233760 (View on PubMed)

McCartney CR, Marshall JC. CLINICAL PRACTICE. Polycystic Ovary Syndrome. N Engl J Med. 2016 Jul 7;375(1):54-64. doi: 10.1056/NEJMcp1514916.

Reference Type BACKGROUND
PMID: 27406348 (View on PubMed)

Azziz R. Polycystic Ovary Syndrome. Obstet Gynecol. 2018 Aug;132(2):321-336. doi: 10.1097/AOG.0000000000002698.

Reference Type BACKGROUND
PMID: 29995717 (View on PubMed)

Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ, Yildiz BO. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016 Aug 11;2:16057. doi: 10.1038/nrdp.2016.57.

Reference Type BACKGROUND
PMID: 27510637 (View on PubMed)

Lindheim L, Bashir M, Munzker J, Trummer C, Zachhuber V, Leber B, Horvath A, Pieber TR, Gorkiewicz G, Stadlbauer V, Obermayer-Pietsch B. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study. PLoS One. 2017 Jan 3;12(1):e0168390. doi: 10.1371/journal.pone.0168390. eCollection 2017.

Reference Type BACKGROUND
PMID: 28045919 (View on PubMed)

Hong X, Qin P, Huang K, Ding X, Ma J, Xuan Y, Zhu X, Peng D, Wang B. Association between polycystic ovary syndrome and the vaginal microbiome: A case-control study. Clin Endocrinol (Oxf). 2020 Jul;93(1):52-60. doi: 10.1111/cen.14198. Epub 2020 May 7.

Reference Type BACKGROUND
PMID: 32311120 (View on PubMed)

Other Identifiers

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8032-20-SMC

Identifier Type: -

Identifier Source: org_study_id

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