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Influence of menstrual cycle phase and serum oestrogen levels on tympanoplasty outcomes in women

Published online by Cambridge University Press:  15 October 2026

Nurcan Yoruk ,
Ayse Nur Aksoy ,
Hazal Altunok ,
Erdi Ozdemir  and
Ozgur Yoruk Open the ORCID record for Ozgur Yoruk [Opens in a new window]
Nurcan Yoruk
Affiliation:
Department of Obstetrics and Gynecology, Erzurum Training and Research Hospital, Türkiye
Ayse Nur Aksoy
Affiliation:
Erzurum Training and Research Hospital, Türkiye
Hazal Altunok
Affiliation:
Otolaryngology, Erzurum Training and Research Hospital, Türkiye
Erdi Ozdemir
Affiliation:
Otolaryngology, Private Clinic, Türkiye
Ozgur Yoruk*
Affiliation:
Otolaryngology, Ataturk University Research Hospital, Türkiye
*
Corresponding author: Ozgur Yoruk; Email: dryoruk_40@hotmail.com
Rights & Permissions [Opens in a new window]

Abstract

Objective

To evaluate whether menstrual cycle phase and serum oestrogen influence tympanoplasty outcomes in premenopausal women.

Methods

Eighty women with small central tympanic membrane perforations (follicular phase, days 1–5, n = 40; ovulatory phase, days 12–16, n = 40) underwent endoscopic transcanal type I tympanoplasty. Outcomes were anatomical success (at 12 weeks) and hearing improvement. Pre-operative serum oestrogen and its predictive value were assessed.

Results

Graft success was higher in the ovulatory than follicular phase (90 vs 70 per cent, p = 0.025). Hearing gain was greater in the ovulatory phase (12.35 ± 4.84 dB vs 4.70 ± 3.92 dB, p < 0.001). Serum oestrogen was significantly higher in the ovulatory phase. Receiver operating characteristic analysis showed modest predictive performance (area under the curve = 0.643).

Conclusion

Tympanoplasty during the ovulatory phase is associated with improved anatomical and functional outcomes, suggesting that endogenous oestrogen benefits tympanic membrane healing.

Keywords

EstrogenMenstrual CycleTympanoplasty

Information

Type
Main Article
Information
The Journal of Laryngology & Otology , First View , pp. 1 - 6
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2026. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED.

Introduction

Tympanoplasty is a commonly performed procedure in otological surgery. The goals of successful tympanoplasty are to eliminate pathology, reconstruct a sound-conducting mechanism within a well-ventilated, mucosa-lined middle-ear cavity and maintain these results over time.Reference Fermi, Maccarrone, Villari, Allevi, Bruschini and Cuda1–Reference Gutierrez, Cabrera, Stout, JW, Isaacson and Roland3 Reported graft success rates range from 65 per cent to 90 per cent. Numerous studies have examined factors associated with surgical outcome, including perforation size and location, infection, Eustachian tube function, smoking status, surgical technique, and local adjunctive treatment.Reference Gutierrez, Cabrera, Stout, JW, Isaacson and Roland3–Reference Reis, Gani, Pereira, Martins, Bento and de Oliveira8

Much of the current understanding of tympanic membrane epithelial structure and repair mechanisms derives from studies of cutaneous wound healing. However, accumulating evidence suggests that tympanic membrane repair differs from skin healing in several important respects. Unlike skin wounds, in which keratinocytes participate later in the repair process, keratinocytes are among the earliest cells involved in sealing tympanic membrane perforations.Reference Dinwoodie, Tucker and Fons9 Due to its intrinsic migratory properties, the epidermal layer of the tympanic membrane is the first to bridge the perforation, whereas repair of the fibrous layer occurs subsequently. The vascular architecture of the tympanic membrane also influences its regenerative response. A key component of tympanic membrane healing is the centripetal migration of epithelial cells originating from the central proliferation zone, which plays a critical role in the restoration of membrane integrity.Reference Lou and Lou10–Reference Harvie, Roy and Gurberg12

Oestrogen has been shown to favourably influence several components of wound healing, including keratinocyte activity, vascular responses and fibroblast function. Previous studies have also examined the effects of topical oestrogen on chronic tympanic membrane perforation healing, reporting enhanced closure rates and improved healing responses. Although studies have considered the effects of oestrogen on tissue repair and tympanic membrane healing using topical application, the relationship between physiological fluctuations in serum oestrogen levels across the menstrual cycle and tympanoplasty outcomes in healthy women remains insufficiently explored.

Given the known role of oestrogen in tissue repair and the cyclical hormonal changes in premenopausal women, it is plausible that menstrual cycle phase and serum oestrogen levels may influence tympanic membrane healing after surgery. To our knowledge, no clinical study has directly investigated the influence of physiological menstrual cycle–related oestrogen fluctuations on tympanoplasty outcomes. Therefore, this study aimed to evaluate whether menstrual cycle phase and serum oestrogen levels influence graft success and hearing outcomes in women undergoing endoscopic tympanoplasty with small central perforations of the pars tensa.

Materials and methods

Study design and ethical approval

This prospective, comparative clinical study investigated the association between serum oestrogen levels and the endoscopic tympanoplasty outcomes in premenopausal women. The study protocol was approved by the Ethics Committee of Erzurum City Hospital, Türkiye (approval number: 282, 3 May 2024). All procedures were conducted in accordance with the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants.

Patient selection

Women with tympanic membrane perforations were initially evaluated at Erzurum City Hospital. Menstrual cycle phase and serum oestrogen levels were determined by an obstetrics and gynaecology specialist working at this institution. Patients who met the study criteria were subsequently referred to the Department of Otolaryngology at Atatürk University for surgical management. All tympanoplasty procedures were performed at Atatürk University by the same otological surgeon. All patients underwent detailed medical history taking, physical examination, otomicroscopic evaluation and baseline audiometric assessment. Perforations were classified as minor (<50 per cent of the tympanic membrane) or major (>50 per cent of the tympanic membrane). Only patients with small central perforations of the pars tensa were included in the study. A total of 150 patients were assessed for eligibility. After exclusion of 50 patients who did not meet the inclusion criteria or declined participation, 100 patients were enrolled in the study and grouped according to menstrual cycle phase. Menstrual cycle phase was determined based on patient-reported menstrual history and confirmed by serum oestrogen measurements obtained on the day of surgery.

Patients were classified as: (1) follicular phase group: surgery performed between days 1 and 5 of the menstrual cycle; and (2) ovulatory phase group: surgery performed between days 12 and 16 of the menstrual cycle.Reference Walker, Dillard, Gonzalez, Haneuse, Eisenberg and Miller13, Reference Abidi, Nili, Serna, Kim, Kim and Convertino14

Only patients whose surgery was scheduled during the early follicular phase (days 1–5) or the ovulatory phase (days 12–16) were eligible for enrolment. Patients undergoing surgery during any other phase of the menstrual cycle were not included in the study.

Venous blood samples were collected on the day of surgery, and serum oestrogen levels were quantified using a commercially available enzyme-linked immunosorbent assay.

Exclusion criteria

In order to obtain a homogeneous study population, patients were excluded if they had acute tympanic membrane perforation; marginal perforation; contralateral ear pathology (perforation, retraction pocket or myringosclerosis); active otorrhoea within the previous three months; otomicroscopic findings suggestive of cholesteatoma (polyps or granulation tissue); previous myringoplasty or tympanoplasty; cleft palate or history of cleft palate repair; obstructive nasal or nasopharyngeal pathology; were smokers; had poorly controlled diabetes mellitus; immunocompromised conditions; menstrual irregularity; infertility or polycystic ovarian syndrome; or refused to participate in the study.

Bone-conduction thresholds were assessed pre-operatively in all patients. Because one aim of the study was to evaluate tympanoplasty-related conductive hearing improvement, patients with clinically significant sensorineural hearing loss were excluded.

Following enrolment, 20 additional patients were excluded because of menstrual phase mismatch at the time of surgery, lack of surgical intervention or missing post-operative audiometric data. Therefore, 80 patients were included in the final analysis (40 in the follicular phase group and 40 in the ovulatory phase group).

Surgical procedure

All patients underwent endoscopic transcanal type I tympanoplasty performed by the same surgeon. After freshening the edges of the perforation, a tragal perichondrial graft was placed using the underlay technique. Gelfoam was used to support the graft in the middle ear and external auditory canal. Post-operative otomicroscopic evaluations and audiometric measurements were performed by clinicians who were not involved in the surgical procedures.

Outcome measures

The primary outcome was anatomical success, defined as complete closure of the tympanic membrane perforation at 12 weeks post-operatively. Patients were followed up on post-operative days 7 and 21, and final graft status was evaluated at 12 weeks using otomicroscopy. The secondary outcome was post-operative hearing improvement.

Pure tone audiometry was performed pre- and post-operatively. Air-conduction thresholds were measured at 0.5, 1, 2 and 4 kHz, and the average of these frequencies was used for analysis. Hearing status was classified according to the World Health Organization classification: normal hearing, 25 dB or less; mild hearing loss, 26–40 dB; and moderate hearing loss, 41–60 dB.Reference Shen, Zhou, Zou, Li, Wang and Liu15

Audiometric gain was calculated as the difference between pre- and post-operative air-conduction thresholds.

Statistical analysis

A total of 150 patients were assessed for eligibility. After excluding 50 patients prior to enrolment, 100 patients were grouped according to menstrual cycle phase. Following additional exclusions due to menstrual phase mismatch, lack of surgical intervention or missing post-operative audiometric data, 80 patients were included in the final analysis (Figure 1).

Figure 1.

Flow diagram of patient inclusion and analysis according to the Consolidated Standards of Reporting Trials (‘CONSORT’) recommendations.

Patient inclusion and analysis for a study, detailing eligibility, exclusions and final analysis groups.

Statistical analyses were performed using SPSS version 20.0 (SPSS, Chicago, Illinois, USA). Continuous variables were expressed as mean ± standard deviation, and categorical variables as number and percentage. Normal distribution of the data was assessed using the Kolmogorov–Smirnov test. Continuous variables between groups were compared using the independent samples t-test. Categorical variables were compared using the chi-square test or Fisher’s exact test. In order to identify predictors of perforation closure, multivariable logistic regression analysis was performed. Results were expressed as odds ratios with 95 per cent confidence intervals (CIs). The relationship between serum oestrogen levels and hearing gain was assessed using Pearson correlation and linear regression analysis. Additionally, receiver operating characteristic curve analysis was performed to evaluate the ability of serum oestrogen levels to predict graft uptake. The area under the curve, optimal cut-off value based on the Youden index, sensitivity and specificity were calculated. A p-value of less than 0.05 was considered statistically significant.

Results and analysis

A total of 80 patients were included in the final analysis, with 40 patients in the follicular phase group and 40 patients in the ovulatory phase group. The two groups were comparable with respect to age, body weight and pre-operative hearing thresholds. Serum oestrogen levels were significantly higher in the ovulatory phase group than in the follicular phase group (p < 0.001), whereas body mass index (BMI) was slightly higher in the ovulatory phase group (Table 1).

Table 1

Baseline demographic and clinical characteristics of patients according to menstrual cycle phase

Serum oestrogen was 33.83 plus or minus 1.04 in the follicular phase and 108.33 plus or minus 0.54 in the ovulatory phase, with p-value less than 0.001. See long description.
Table 1 Long description

Baseline characteristics are reported for two groups, follicular phase with n equals 40 and ovulatory phase with n equals 40, with a p-value column for each variable. Age in years was 28.15 plus or minus 6.84 for follicular and 27.45 plus or minus 6.83 for ovulatory, p-value 0.648. Weight in kilograms was 61.46 plus or minus 4.13 for follicular and 61.55 plus or minus 2.93 for ovulatory, p-value 0.913. Body mass index in kilograms per meter squared was 23.72 plus or minus 1.11 for follicular and 24.40 plus or minus 1.26 for ovulatory, p-value 0.013. Pre-operative hearing threshold in decibels was 34.65 plus or minus 3.05 for follicular and 34.17 plus or minus 2.99 for ovulatory, p-value 0.484.

Note: Values are presented as mean ± standard deviation. Comparisons between groups were performed using the independent samples t-test. BMI = body mass index

Two outcome measures were evaluated: anatomical success and hearing improvement. Anatomical success, defined as complete closure of the tympanic membrane perforation, was achieved in 28 patients (70 per cent) in the follicular phase group and in 36 patients (90 per cent) in the ovulatory phase group, a difference that was statistically significant (p = 0.025).

Post-operative hearing outcomes also differed between the groups. In the follicular phase group, the mean air-conduction threshold decreased from 34.65 ± 3.05 dB pre-operatively to 29.95 ± 4.63 dB post-operatively, corresponding to an audiometric gain of 4.70 ± 3.92 dB. In the ovulatory phase group, the mean air-conduction threshold decreased from 34.17 ± 2.99 dB to 21.83 ± 6.45 dB, corresponding to an audiometric gain of 12.35 ± 4.84 dB. The difference in hearing improvement between the groups was highly significant (p < 0.001). Pre- and post-operative hearing threshold values are presented in Figure 2. Overall, audiological success was significantly higher in the ovulatory phase group than in the follicular phase group (p < 0.001).

Figure 2.

Pre- and post-operative air-conduction hearing thresholds (dB HL) in the follicular and ovulatory phase groups.

A line graph comparing mean hearing threshold before and after operation across patients, with repeated paired values and wide variation between patients. See long description.
Figure 2 Long description

Mean hearing threshold (dB HL) A line graph with two plotted series and vertical connectors between paired points for each patient. The x-axis is labeled, Patient, with tick labels from 1 to 80. The y-axis is labeled, Mean hearing threshold (dB HL), ranging from 0 to 40 with labeled ticks at 0, 10, 20, 30 and 40. A legend shows two markers: Pre-Operative hearing threshold and Post-Operative hearing threshold. For each patient number, two points are plotted, one for pre-operative and one for post-operative, connected by a vertical line segment. Values span roughly from about 10 to about 40 on the y-axis across all patients. Many paired points show the post-operative point below the pre-operative point, while some pairs are close together. Two bracketed group labels appear below the x-axis: Follicular patients on the left portion of the patient range and Ovulatory patients on the right portion of the patient range.

Receiver operating characteristic curve analysis demonstrated that serum oestrogen level had modest discriminative ability for predicting graft uptake, with an area under the curve of 0.643. The optimal cut-off value was 34.9 pg/ml, yielding a sensitivity of 65.6 per cent and a specificity of 75.0 per cent (Figure 3).

Figure 3.

Receiver operating characteristic (ROC) curve showing the performance of serum oestrogen level for predicting graft uptake after tympanoplasty. AUC = area under the curve.

A line graph showing a receiver operating characteristic curve for oestrogen predicting graft closure.

Multivariable logistic regression analysis identified several predictors of graft success. Surgery performed during the ovulatory phase was a significant independent predictor of successful graft uptake (odds ratio = 11.71, 95 per cent CI = 2.17–63.27, p = 0.004). Serum oestrogen level was also significantly associated with graft success (odds ratio = 1.03, 95 per cent CI = 1.01–1.06, p = 0.004). Because menstrual cycle phase and serum oestrogen levels were highly correlated, they were not included simultaneously in the same regression model in order to avoid multicollinearity. In contrast, higher BMI showed a significant negative association with graft success (odds ratio = 0.37, 95 per cent CI = 0.19–0.70, p = 0.002), whereas age was not a significant predictor (p = 0.863) (Table 2).

Table 2

Multivariable logistic regression analysis identifying predictors of successful graft uptake following tympanoplasty

Ovulatory phase surgery has an odds ratio of 11.71 for successful graft uptake, with BMI and serum oestrogen also significant and age not significant. See long description.
Table 2 Long description

Multivariable logistic regression results are reported for successful graft uptake, with columns for odds ratio, 95% CI, and p value. Ovulatory phase surgery has an odds ratio of 11.71, 95% CI 2.17 to 63.27, p value 0.004 with an asterisk. Age has an odds ratio of 1.01, 95% CI 0.91 to 1.11, p value 0.863. BMI has an odds ratio of 0.37, 95% CI 0.19 to 0.70, p value 0.002 with an asterisk. Serum oestrogen marked with a dagger has an odds ratio of 1.03, 95% CI 1.01 to 1.06, p value 0.004 with an asterisk.

* Indicates statistical significance.

† Because menstrual cycle phase and serum oestrogen levels were strongly correlated, oestrogen was evaluated in a separate adjusted model. CI = confidence interval; BMI = body mass index

Discussion

The present study demonstrated that tympanoplasty performed during the ovulatory phase of the menstrual cycle was associated with significantly better anatomical and functional outcomes than procedures performed during the follicular phase in otherwise healthy premenopausal women. Both graft uptake rates and post-operative hearing improvements were notably higher in the ovulatory phase group. Serum oestrogen levels were significantly elevated during this phase, and higher oestrogen concentrations were associated with improved tympanic membrane healing and greater audiometric gain. These findings suggest that endogenous hormonal status may meaningfully contribute to variations in surgical outcomes following tympanoplasty.

Histologically, tympanic membrane healing involves three overlapping stages: inflammatory, proliferative and remodelling.Reference Lou and Lou16–Reference Heitmann, Scheffler, Abrams, Plontke, Rahne and Mlynski21 The inflammatory phase is characterised by epithelial hyperplasia and keratin accumulation at the perforation margins. Rapid cellular proliferation begins within hours and is accompanied by the accumulation of interstitial fluid, lymph and blood. The proliferative phase follows, during which epithelial cells migrate centripetally across the perforation, while fibroblast activity, angiogenesis and extracellular matrix deposition increase, leading to restoration of tympanic membrane integrity. Finally, the remodelling phase involves gradual normalisation of epithelial thickness and membrane organisation, although a thicker fibrous layer or residual scarring may persist for several months. Small tympanic membrane perforations may close rapidly within days, whereas larger perforations require more prolonged healing.Reference Heitmann, Scheffler, Abrams, Plontke, Rahne and Mlynski21

Experimental studies have demonstrated that oestrogen plays a critical role in tissue repair. It promotes keratinocyte proliferation, enhances epithelialisation, modulates fibroblast function, and reduces oxidative stress and apoptosis.Reference Mukai, Horike, Meguro Horike, Yamamoto, Yamamoto and Takahashi22–Reference Böhm, Stegemann, Paus, Schneider, Langan and Tobin25 Oestrogen also regulates extracellular matrix production, angiogenesis and co-ordinated cellular migration, all of which are crucial for successful tympanic membrane closure.Reference Rzepecki, Murase, Juran, Femia, Munoz and Cohen26–Reference Xu, Chen, Guo, Li, Zhang and Wang28 While prior studies primarily focused on topical or systemic oestrogen therapy to improve tympanic membrane healing,Reference Barati, Abtahi, Hashemi, Safari, Khosravi and Kianoush29 our study demonstrates that physiological fluctuations in endogenous oestrogen across the menstrual cycle can similarly influence surgical outcomes, underscoring the potential clinical relevance of hormonal status in premenopausal women.

In this study, serum oestrogen levels were significantly higher during the ovulatory phase (mean, 108.33 ± 0.54 pg/ml) than during the follicular phase (mean, 33.83 ± 1.04 pg/ml), and higher levels were associated with both improved graft uptake and greater audiometric gain. Although all patients had small central perforations, conductive hearing loss associated with tympanic membrane perforations is determined not only by perforation size but also by perforation location, residual tympanic membrane mobility, middle-ear volume and individual middle-ear acoustic characteristics. Consequently, patients with similar perforation sizes may demonstrate different degrees of conductive hearing loss. Furthermore, patients with cholesteatoma, ossicular abnormalities, active infection, previous ear surgery and clinically significant sensorineural hearing loss were excluded from the present study. Receiver operating characteristic analysis demonstrated a moderate discriminative ability of oestrogen levels for predicting graft success (area under the curve = 0.643), with an optimal cut-off value of 34.9 pg/ml, suggesting that serum oestrogen, while not a standalone predictor, contributes to post-operative healing alongside other patient- and surgery-related factors. The relatively modest discriminative performance of serum oestrogen levels observed in the receiver operating characteristic analysis suggests that graft healing is influenced by multiple biological mechanisms. While oestrogen may enhance epithelial migration, angiogenesis and fibroblast activity, other factors such as local vascular supply, inflammatory responses, extracellular matrix remodelling, genetic variability in wound-healing pathways and subtle differences in Eustachian tube function may also contribute to surgical outcome. Therefore, oestrogen should be considered a contributing rather than an exclusive determinant of graft success.

Furthermore, our multivariable analysis revealed that higher BMI was inversely associated with graft success, reflecting the broader impact of systemic factors on tissue repair. Obesity has been linked to impaired wound healing due to altered inflammatory responses, microvascular dysfunction and changes in collagen metabolism, which may compromise tympanic membrane repair in addition to local surgical factors.

Mechanistically, the favourable outcomes observed in the ovulatory phase group may reflect the biologically favourable regenerative environment created by higher circulating oestrogen levels, including enhanced epithelial migration, fibroblast activity and vascular responses. Oestrogen also modulates inflammatory cytokines, reduces neutrophil infiltration and promotes collagen deposition, thereby supporting both structural integrity and functional recovery of the tympanic membrane.Reference Böhm, Stegemann, Paus, Schneider, Langan and Tobin25–Reference Xu, Chen, Guo, Li, Zhang and Wang28, Reference Gilliver30–Reference Hardman and Ashcroft32 These mechanisms may explain the higher graft success and improved hearing thresholds observed in patients undergoing tympanoplasty during the ovulatory phase.

Clinically, these findings indicate that menstrual cycle phase could be considered a simple, non-invasive and cost-free factor to optimise tympanoplasty outcomes. Timing surgery during hormonally favourable phases may enhance graft uptake and functional recovery, particularly in otherwise healthy premenopausal women. Although additional studies are required, these results raise the possibility of integrating menstrual cycle timing into pre-operative planning, similar to other recognised prognostic factors such as perforation size, middle-ear status and patient co-morbidities.

Tympanoplasty performed during the ovulatory phase may be associated with higher graft success rates and greater post-operative hearing improvement. Endogenous hormonal status, particularly elevated oestrogen levels, may positively influence tympanic membrane healing. Consideration of menstrual cycle phase may represent a novel, clinically relevant factor in surgical planning for premenopausal women, although further large-scale studies are needed to confirm these findings.

This study has several limitations. First, the sample size was relatively limited, potentially affecting generalisability. However, only a restricted number of clinically relevant variables were included in multivariable models, to reduce the risk of overfitting. Second, while serum oestrogen levels were measured, other hormonal or inflammatory biomarkers that may influence wound healing were not assessed. Third, the observational design limits the ability to establish a direct causal relationship between hormonal status and surgical outcomes. Finally, the study population consisted exclusively of premenopausal women with small central tympanic membrane perforations, which may limit applicability to other patient groups.

  • • Tympanoplasty success is influenced by several patient- and disease-related factors

  • • Oestrogen has been shown experimentally to promote wound healing and tympanic membrane repair

  • • Tympanoplasty performed during the ovulatory phase resulted in significantly higher graft success and greater hearing improvement than surgery performed during the follicular phase

  • • Physiological serum oestrogen levels may represent a clinically relevant factor when planning tympanoplasty in premenopausal women

Conclusion

This study provides important preliminary evidence that menstrual cycle phase and endogenous oestrogen levels may influence tympanic membrane healing after tympanoplasty.

Data availability statement

Data may be provided on reasonable request to the corresponding author.

Competing interests

None declared

Ethical standards

The authors assert that all procedures contributing to this work comply with the ethical standards of the Ethics Committee of Erzurum City Hospital, Erzurum, Türkiye, and with the Helsinki Declaration of 1975, as revised in 2008.

Footnotes

Ozgur Yoruk takes responsibility for the integrity of the content of the paper

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Figure 0

Figure 1. Flow diagram of patient inclusion and analysis according to the Consolidated Standards of Reporting Trials (‘CONSORT’) recommendations.

Figure 1

Table 1 Baseline demographic and clinical characteristics of patients according to menstrual cycle phaseTable 1 long description.

Figure 2

Figure 2. Pre- and post-operative air-conduction hearing thresholds (dB HL) in the follicular and ovulatory phase groups.Figure 2 long description.

Figure 3

Figure 3. Receiver operating characteristic (ROC) curve showing the performance of serum oestrogen level for predicting graft uptake after tympanoplasty. AUC = area under the curve.

Figure 4

Table 2 Multivariable logistic regression analysis identifying predictors of successful graft uptake following tympanoplastyTable 2 long description.