Objective:
Acute COVID-19 infection is associated with small temporary menstrual cycle length increases, possibly driven by cytokine-mediated disruption of the hypothalamic-pituitary-ovarian axis.1 However, little is known about menstrual patterns among individuals experiencing post-acute sequelae of COVID-19 (“long COVID”), which is associated with prolonged activation of proinflammatory cytokine signaling pathways.2 Most evidence of menstrual changes following long COVID comes from retrospective self-reported data.3, 4 This study used prospectively collected menstrual cycle data to compare changes among individuals experiencing acute and long COVID and characterize long COVID symptoms among a healthy population with regular cycles.
Study Design:
We combined menstrual cycle data from a digital birth control application, Natural Cycles, with a survey on self-reported timing and type (acute versus long) of initial COVID-19 infection and long COVID symptoms. We examined six consecutive cycles starting with the infection cycle, comparing COVID groups’ adjusted changes in cycle and menses length from pre-infection means (estimated using linear regression models adjusted for age group, parity, and body mass index category), and the proportion with anovulatory cycles and clinically significant changes in cycle length (≥8 days).5 We created bleeding volume heatmaps for the first ten days of the three cycles before and after infection, by disease type, and described long COVID symptoms (see Supplemental Methods for details).
Results:
Our final sample included 1,624 individuals: 1,444 acute and 180 long COVID. Our sample was primarily under age 35 (n=1,197; 73.7%) and based in the United States or Canada (n=928; 57.1%). Characteristics did not differ by disease type (See Supplemental Results). Median infection date was 12/25/2022 for acute and 03/10/2023 for the long COVID group.
Both acute and long COVID groups experienced an adjusted cycle length increase of approximately half a day during the first infection cycle: 0.56 days (95% CI: 0.34 – 0.78) and 0.46 days (95% CI: −0.16 – 1.08), respectively; the groups were not statistically different (p=0.764; Table 1A). We observed no significant changes from the pre-infection cycle length mean for either group in infection cycles two through six. There were no significant changes in menses length in any infection cycles for either group, and the groups did not differ in the proportion of anovulatory cycles or clinically significant changes in cycle length for any infection cycle (Table 1B–1D). Visual analysis of bleeding volume did not show distinct patterns before and after infection in both COVID groups. Median duration of long COVID symptoms was 6 months (IQR 4 – 15; TABLE S2) and median number of reported symptoms was 5 (IQR 3.5 – 7); the most commonly reported symptoms were fatigue (78.9%), brain fog (74.4%), and post-exercise exhaustion (64.4%).
Table 1:
Unadjusted and adjusted changes in menstrual cycle length and menses length (in days; Panels A and B, respectively), and the proportion of individuals with a clinically significant (≥ 8 days) change in cycle length from pre-infection mean (Panel C) and individuals with anovulatory cycles (Panel D), for the 6 cycles starting with COVID-19 infection, by disease type (1st infection cycle n = 1,444 for Acute COVID and 180 for Long COVID). Cycle length changes are calculated as the difference from the mean of the 3 pre-infection cycles.
| Unadjusted | Adjusted* | |||||||
|---|---|---|---|---|---|---|---|---|
| Panel | Outcome | Infection cycle # | Acute COVID | Long COVID | p-value** | Acute COVID | Long COVID | p-value** |
| A | Change in menstrual cycle length (days) | 1 | 0.55 (0.33 – 0.77) | 0.49 (−0.13 – 1.11) | 0.857 | 0.56 (0.34 – 0.78) | 0.46 (−0.16 – 1.08) | 0.764 |
| 2 | 0.13 (−0.09 – 0.34) | −0.01 (−0.62 – 0.60) | 0.684 | 0.13 (−0.09 – 0.34) | −0.02 (−0.63 – 0.59) | 0.656 | ||
| 3 | 0.16 (−0.07 – 0.39) | −0.32 (−0.96 – 0.33) | 0.175 | 0.16 (−0.07 – 0.39) | −0.37 (−1.01 – 0.28) | 0.131 | ||
| 4 | 0.20 (−0.04 – 0.43) | 0.11 (−0.58 – 0.79) | 0.808 | 0.20 (−0.04 – 0.44) | 0.06 (−0.62 – 0.75) | 0.711 | ||
| 5 | −0.12 (−0.33 – 0.10) | 0.16 (−0.48 – 0.80) | 0.420 | −0.11 (−0.33 – 0.10) | 0.14 (−0.50 – 0.78) | 0.467 | ||
| 6 | −0.06 (−0.29 – 0.18) | 0.17 (−0.54 – 0.89) | 0.548 | −0.05 (−0.29 – 0.18) | 0.15 (−0.56 – 0.86) | 0.594 | ||
| B | Change in menses length (days) | 1 | −0.04 (−0.11 – 0.03) | 0.08 (−0.12 – 0.28) | 0.277 | −0.04 (−0.11 – 0.03) | 0.08 (−0.12 – 0.28) | 0.290 |
| 2 | 0.06 (−0.01 – 0.12) | 0.06 (−0.12 – 0.24) | 0.999 | 0.06 (−0.01 – 0.12) | 0.06 (−0.13 – 0.24) | 0.997 | ||
| 3 | 0.05 (−0.03 – 0.14) | 0.03 (−0.20 – 0.26) | 0.851 | 0.05 (−0.03 – 0.14) | 0.03 (−0.19 – 0.26) | 0.867 | ||
| 4 | −0.02 (−0.10 – 0.05) | −0.13 (−0.35 – 0.08) | 0.332 | −0.02 (−0.10 – 0.05) | −0.13 (−0.35 – 0.08) | 0.333 | ||
| 5 | −0.04 (−0.12 – 0.03) | −0.08 (−0.30 – 0.14) | 0.728 | −0.04 (−0.12 – 0.03) | −0.09 (−0.31 – 0.13) | 0.689 | ||
| 6 | 0.01 (−0.10 – 0.13) | −0.01 (−0.36 – 0.34) | 0.892 | 0.01 (−0.10 – 0.13) | 0.00 (−0.35 – 0.35) | 0.944 | ||
| C | Proportion with ≥ 8-day change in cycle length | 1 | 69/1,444 (4.7%) | 10/180 (5.6%) | 0.585 | |||
| 2 | 61/1,427 (4.3%) | 10/178 (5.6%) | 0.437 | |||||
| 3 | 51/1,336 (3.8%) | 6/169 (3.6%) | 1.000 | |||||
| 4 | 52/1,246 (4.2%) | 9/150 (6.0%) | 0.291 | |||||
| 5 | 38/1,167 (3.3%) | 7/133 (5.3%) | 0.214 | |||||
| 6 | 50/1,088 (4.6%) | 5/119 (4.2%) | 1.000 | |||||
| D | Proportion with anovulatory cycle | 1 | 31/1,444 (2.2%) | 3/180 (1.7%) | 1.000 | |||
| 2 | 24/1,427 (1.7%) | 4/178 (2.3%) | 0.542 | |||||
| 3 | 21/1,336 (1.6%) | 6/169 (3.6%) | 0.112 | |||||
| 4 | 15/1,246 (1.2%) | 4/150 (2.7%) | 0.139 | |||||
| 5 | 19/1,167 (1.6%) | 0/133 (0.0%) | 0.248 | |||||
| 6 | 18/1,088 (1.7%) | 3/119 (2.5%) | 0.454 | |||||
Models are adjusted for age group, parity, and body mass index category.
p-value for differences between COVID-19 disease types: from linear regression models for changes in menstrual cycle and menses length; from Fisher’s exact test for proportion of individuals with a clinically significant (≥8 days) change in cycle length.
Conclusion:
Small (<1-day) increases in menstrual cycle length during the initial infection cycle did not differ between individuals with acute and long COVID or persist in subsequent cycles. No other changes to menstrual cycle characteristics were observed in either group for any of the six infection cycles. Menstrual cycle changes from other viral infections are not known, but our finding of small transitory increases in menstrual cycle length during the initial COVID-19 infection cycle are in line with previous work comparing to an uninfected cohort1, 6 However, like those studies, these findings may not be generalizable to all populations. While previous studies using retrospective self-reported changes to menstrual cycle characteristics, which may be subject to recall bias, have identified menstrual cycle irregularities during long COVID infection,3, 4 we found no evidence of sustained cycle changes after the initial cycle of infection among this cohort of relatively young individuals with regular menstrual cycles.
Supplementary Material
Funding
This study was supported by grant NICHD089957 from the US National Institute of Child Health and Human Development (PI, Dr. Edelman).
Conflict of Interest Disclosure
ERB: honorarium and grants Society of Family Planning (SFP). BGD: grants National Institutes of Health (NIH); honorarium American College of Obstetricians and Gynecologists; support SFP; travel costs, serving as Editor in Chief at Contraception. AvL and EB: employed by NaturalCycles. AE: grants NIH, Organon, HRAPharma,Gates Foundation; royalties Contemporary Forums and UpToDate Inc; honoraria Medscape and FHI360; travel costs World Health Organization, Centers for Disease Control and Prevention.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
References
- 1.Alvergne A, Boniface E, Darney B, et al. Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination. Obstet Gynecol 2024;143:83–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Aid M, Boero-Teyssier V, McMahan K, et al. Long COVID involves activation of proinflammatory and immune exhaustion pathways. Nature Immunology 2026;27:61–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Maham S, Yoon MS. Clinical Spectrum of Long COVID: Effects on Female Reproductive Health. Viruses 2024;16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Maybin JA, Walker C, Watters M, et al. The potential bidirectional relationship between long COVID and menstruation. Nature Communications 2025;16:8187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Munro MG, Critchley HOD, Fraser IS. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet 2018;143:393–408. [DOI] [PubMed] [Google Scholar]
- 6.Hariton E, Morris JR, Ho K, Chen C, Cui E, Cedars MI. The effect of the coronavirus disease 2019 vaccine and infection on menstrual cycle length: an analysis of 12 months of continuous menstrual cycle data from 5,314 participants. Fertility and Sterility 2023;120:387–88. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.