Hua, X., Cao, Y., Morgan, D. M., Miller, K., Chin, S. M., Bellavance, D., & Khalili, H. (2022). Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome. Journal of medical microbiology, 71(4). https://doi.org/10.1099/jmm.0.001512
Hua X, Cao Y, Morgan DM, Miller K, Chin SM, Bellavance D, Khalili H. Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome. Journal of medical microbiology. 2022;71(4). doi:10.1099/jmm.0.001512
Hua, X., et al. "Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome." Journal of medical microbiology, vol. 71, no. 4, 2022.
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Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.
Zhao Q et al., 2023·The Science of the total environment
The health risk of microplastics (MPs) is a growing global concern. Evidence of reproductive health damage caused by the accumulation of MPs in males is still lacking. In the present study, 6 testis and 30 semen samples were collected, and MPs were detected using both pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LD-IR). The results showed that MPs were detected in both testis and semen, with an average abundance of 0.23 ± 0.45 particles/mL in semen and 11.60 ± 15.52 particles/g in testis. Microplastics in the testis were composed of polystyrene (PS) with 67.7 %, while polyethylene (PE) and polyvinyl chloride (PVC) were the predominant polymers in semen. Compared to fragments, fiber, and film detected in semen, the fragment was the main shape the in testis. The sizes of these microplastics ranged from 21.76 μm to 286.71 μm, and most (67 % and 80.6 %) were 20-100 μm in semen and testis. In summary, this study revealed for the first time that MPs pollute the human male reproductive system and that various MP characteristics appear in different regions, which provides critical information and basic data for the risk assessment of MPs to human health.
Corona LE et al., 2015·American journal of obstetrics and gynecology
We sought to analyze use of alternative treatments and pathology among women who underwent hysterectomy in the Michigan Surgical Quality Collaborative. Perioperative hysterectomy data including demographics, preoperative alternative treatments, and pathology results were analyzed from 52 hospitals participating in the Michigan Surgical Quality Collaborative from Jan. 1 through Nov. 8, 2013. Women who underwent hysterectomy for benign indications including uterine fibroids, abnormal uterine bleeding (AUB), endometriosis, or pelvic pain were eligible. Pathology was classified as "supportive" when fibroids, endometriosis, endometrial hyperplasia, adenomyosis, adnexal pathology, or unexpected cancer were reported and "unsupportive" if these conditions were not reported. Multivariable analysis was done to determine independent associations with use of alternative treatment and unsupportive pathology. Inclusion criteria were met by 56.2% (n = 3397) of those women who underwent hysterectomy (n = 6042). There was no documentation of alternative treatment prior to hysterectomy in 37.7% (n = 1281). Alternative treatment was more likely to be considered among women aged <40 years vs those aged 40-50 and >50 years (68% vs 62% vs 56%, P < .001) and among women with larger uteri. Unsupportive pathology was identified in 18.3% (n = 621). The rate of unsupportive pathology was higher among women age <40 years vs those aged 40-50 and >50 years (37.8% vs 12.0% vs 7.5%, P < .001), among women with an indication of endometriosis/pain vs uterine fibroids and/or AUB, and among women with smaller uteri. This study provides evidence that alternatives to hysterectomy are underutilized in women undergoing hysterectomy for AUB, uterine fibroids, endometriosis, or pelvic pain. The rate of unsupportive pathology when hysterectomies were done for these indications was 18%.
Hua X et al., 2012·International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
[OBJECTIVE] To evaluate the effectiveness of autologous platelet-rich plasma (PRP) applications in the treatment of benign cervical ectopy. [METHODS] Symptomatic women with benign cervical ectopy (n=120) were randomized to a PRP or a laser group. In the PRP group, PRP was applied twice on the cervical erosion with a 1-week interval. In the laser group, an Nd-YAG laser was used once for tissue vaporization. [RESULTS] The complete cure rates were 93.7% for the PRP and 92.4% for the laser group (P>0.05). The mean time to re-epithelialization was significantly shorter in the PRP (6.41 ± 2.05 weeks) than in the laser group (8.28 ± 1.72 weeks) (P<0.01). The rate of adverse treatment effects (i.e. vaginal discharge or vaginal bleeding) was much lower in the PRP than that in the laser group (P<0.01) and the effects were milder. Eleven patients in the PRP group had mild or moderate vaginal bleeding after treatment but none had heavy bleeding. Of 25 patients with vaginal bleeding in the laser group, 2 had heavy bleeding necessitating tamponade. [CONCLUSION] Autologous PRP applications appear promising for the treatment of cervical ectopy in symptomatic women, as they generate a shorter tissue healing time and milder adverse effects than laser treatment.
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This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.
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Combined oral contraceptives (COCs) possess the ability to alter the normal composition of the gut microbiome and the permeability of the gastrointestinal (GI) tract, which may cause both gut-related and non-gut-related complications. The gut-estrogen axis examines the relationship between estrogens (particularly the active form, estradiol) and the gastrointestinal system and can be attributed to the maintenance of the estrobolome and circulating estradiol levels. The gut-brain axis involves the relationship between the brain and the gastrointestinal system and can be attributed to the gut microbiome in relation to the enteric nervous system (ENS) and serotonin levels. Overall, the introduction of exogenous hormones into an endogenous environment alters the normal balance of both hormones and bacteria. Currently, there is a gap in knowledge regarding the link between COCs and mental health complications such as anxiety and depression, and the diversity in these complications may be related to different types of COCs, their composition, and variations in study populations. This article reviews existing evidence from animal and human studies on the role of COCs in the development of mental health issues through their impact on the gut microbiome.
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Brito J et al., 2025·Journal of applied physiology (Bethesda, Md. : 1985)·Free to read
Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (n = 12 per group; 22 ± 2 yr, 24 ± 4 kg/m2 vs. 22 ± 4 yr, 23 ± 4 kg/m2; Ps ≥ 0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. α-diversity (microbial richness and evenness) was assessed using the Shannon index whereas β-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (days 1-5) to mid-cycle (days 12-17) in both groups (time effect Ps ≤ 0.01), with greater changes in Control (Ps ≤ 0.046) than HBC (Ps ≥ 0.231). Although no menstrual phase effect was observed on either diversity measure (Ps ≥ 0.473), β-diversity differed between Control and HBC groups (P = 0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted Ps ≤ 0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.NEW & NOTEWORTHY This study is the first to investigate interactions between hormonal contraception and the gut microbiota in a cohort of physically active young females across the menstrual cycle. Our findings suggest that hormonal contraception may influence gut microbiota composition, potentially through a reduced relative abundance of short-chain fatty acid-producing taxa. Experimental studies are needed to confirm these associations and explore their potential implications for metabolism, health, and performance.
Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women's health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development of conditions discussed herein: obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study.
PMID 35452382 35452382 DOI 10.1099/jmm.0.001512 10.1099/jmm.0.001512 Hua et al. 2022, Hua 2022
Cite this article
Hua, X., Cao, Y., Morgan, D. M., Miller, K., Chin, S. M., Bellavance, D., & Khalili, H. (2022). Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome. Journal of medical microbiology, 71(4). https://doi.org/10.1099/jmm.0.001512
Hua X, Cao Y, Morgan DM, Miller K, Chin SM, Bellavance D, Khalili H. Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome. Journal of medical microbiology. 2022;71(4). doi:10.1099/jmm.0.001512
Hua, X., et al. "Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome." Journal of medical microbiology, vol. 71, no. 4, 2022.
Keywords
estradiol, human gut microbiome, oral contraceptive, sex hormone, sex hormone-binding globulin, shotgun metagenomic sequencing