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Is Long COVID the Match That Will Finally Light a Fire Under Research Into Women’s Reproductive Health?

is-long-covid-the-match-that-will-finally-light-a-fire-under-research-into-women’s-reproductive-health?
Is Long COVID the Match That Will Finally Light a Fire Under Research Into Women’s Reproductive Health?

When Letícia Soares came down with COVID-19 in April 2020, her life veered off course. Soares, who was studying the evolution of wildlife diseases for her postdoc in Canada, was bedbound for 32 days. Extreme fatigue and other symptoms worsened over the following year, leading to a long COVID diagnosis that—to this day—has kept her mostly confined to her house.

“Sometimes just standing line in the pharmacy is enough to put me in bed. I can’t do anything for several days,” she says.

Due to reduced mobility and symptoms including severe fatigue, pain, and migraines, Soares was unable to continue her studies. Her visa was revoked, and she was forced to return to her home country of Brazil in November 2021.


Experts In This Article

  • Alba Azola, MD, co-director of the Johns Hopkins Post-Acute COVID-19 Team and assistant professor of physical medicine and rehabilitation
  • Beth Pollack, research scientist at the Massachusetts Institute of Technology’s Department of Biological Engineering
  • Kathryn Terry, ScD, associate epidemiologist in the OB/GYN Epidemiology Center at Brigham and Women’s Hospital in Boston
  • Letícia Soares, PhD, long COVID activist and researcher
  • Victoria Male, PhD, senior lecturer in reproductive immunology at Imperial College London

Soares began logging her symptoms. Among the more than 200 she observed, the bizarre changes in her menstrual cycle caught her attention. She’d had a Mirena intrauterine device (IUD) since 2012, replacing it in 2018, and was among the 20 percent of people with the device who stopped having a period. But a year and a half after getting COVID, Soares’ periods mysteriously returned, with heavy bleeding and excruciating cramps. She also noted that her long COVID symptoms seemed to worsen around her period.

“It’s almost like somebody got the controls, and all the different types of pain that I feel with COVID just level up,” during that time of the month, she says.

Soares, who holds a PhD in biology and is a patient-researcher with the long COVID activist group Patient-Led Research Collaborative (PLRC), decided to do some digging. “There was my just intrinsic curiosity as a scientist of just, ‘What is going on?’” she says. With the support of the PLRC, she and several other researchers published a literature review1 in April 2023 suggesting long COVID could be associated with reproductive health issues in people with ovaries, from endometriosis to fertility issues and more.

Soares is far from the only one who’s noticed a link. Alba Azola, MD, the co-director of the Johns Hopkins Post-Acute COVID-19 Team and an assistant professor of physical medicine and rehabilitation, says irregular periods and menstrual-related symptom flares are “common” in her long COVID patients. Other patients, she says, experience perimenopausal symptoms, like hot flashes, that suddenly begin in their late 30s or early 40s—several years earlier than the average onset.

Victoria Male, PhD, a senior lecturer in reproductive immunology at Imperial College London, in the United Kingdom, was studying2 the effects of COVID vaccination on the menstrual cycle when a flood of long COVID patients began reaching out to tell her their symptoms got worse during their periods, too. This struck her, she says, because symptoms of autoimmune diseases like multiple sclerosis, lupus, and inflammatory bowel disease also fluctuate with the menstrual cycle.

“I was like, hmm, that’s really interesting,” she says. “And it might make sense with what we know about immunology and what we think about long COVID. So let’s try to study this formally.”

What we know so far about long COVID and reproductive health

Long COVID appears to affect roughly 3twice as many women as men, especially premenopausal women4. To Beth Pollack, a co-author of Soares’s review and a research scientist at the Massachusetts Institute of Technology’s Department of Biological Engineering, this “suggests5 that sex hormones or pathological female immune responses to infection may play important roles.”

Pollack studies infection-associated chronic illnesses including long COVID, and the lab where she works, the MIT Tal Research Group, is looking into sex differences in immunity.

Most studies so far involve only a few or even just single patients, so we’re far from having a smoking gun. But some 2021 observational research6 suggests people’s long COVID symptoms do seem to worsen just before or during their periods. One 2022 study7 found that around half of the nearly 500 women included experienced changes in their menstrual cycles after having COVID, including irregular cycles and heavier periods.

Male is currently working on two studies to explore this observation. In one—part of a larger ongoing study on the immunological effects of long COVID—people with and without long COVID will give blood samples throughout their menstrual cycles, so researchers can track fluctuations in their immune markers. In a second study, people with and without long COVID will log their periods alongside how they generally feel and any other symptoms they’re having (breathlessness, brain fog, rashes, fatigue, etc.). Male and her team hope this will help to identify patterns and confirm if and how much long COVID affects the menstrual cycle-related changes people notice in their health.

Other research suggests long COVID might have consequences for fertility. One January 2022 study8 of 80 women undergoing assisted reproductive technology procedures (such as IVF) found that a history of COVID-19 decreased the chances of successfully retrieving a mature egg. Some case 9reports10 have also linked long COVID to primary ovarian insufficiency (POI, also known as premature menopause), or a loss of normal ovary function before the age of 40. In addition to infertility, POI may be associated with chronic conditions including osteoporosis and heart disease.

Kathryn Terry, ScD, an associate epidemiologist in the OB/GYN Epidemiology Center at Brigham and Women’s Hospital in Boston, became interested in researching the link between long COVID and endometriosis because the conditions share symptoms, notably fatigue. In endometriosis, tissue that normally lines the inside of the uterus grows outside of it, mainly in the ovaries and fallopian tubes. Beyond painful and heavy periods, endometriosis has been linked to infertility and a higher risk11 of pregnancy complications such as preeclampsia, preterm birth, and placental abruption.

Terry’s study12, published last March in the American Journal of Obstetrics and Gynecology, looked at 386 women who were diagnosed with endometriosis before the pandemic and found they were 22 percent more likely to have long COVID than those without an endometriosis diagnosis. This doesn’t mean endometriosis causes long COVID, but it confirms earlier research13 suggesting it could be a risk factor.

“Considering the history of research in reproductive health for women and nonbinary people,” or, more accurately, the lack thereof, “I think we have to fight for recognition that we have an issue that is urgent and worth investigating.” —Letícia Soares, PhD, long COVID activist and researcher

Theories about long COVID’s link to reproductive health

Plenty of yet-unproven theories might eventually help explain why people with ovaries tend to have specific health effects following a COVID infection. Both Male and Pollack say it’s possible that a live but undetected virus may lurk in the body. This persistent infection could cause some people’s immune systems to produce chronic inflammation that keeps the body from repairing itself and drives long COVID and reproductive health issues.

Similarly, because symptoms of autoimmune conditions also fluctuate with the menstrual cycle, Male says long COVID might actually be an autoimmune condition. Other researchers have been exploring a potential COVID-autoimmune link; some have found that people are more likely to be diagnosed with an autoimmune condition, such as rheumatoid arthritis, lupus, or irritable bowel disease, after having COVID.

Immune system differences might play a role as well: People with endometriosis have more inflammation and immune dysregulation, for example, which “could be contributing to their higher risk of having long COVID,” says Terry. (Researchers are also exploring16 whether, similar to long COVID, endometriosis might be caused by an infection.)

The female sex hormones estrogen and progesterone are known to17 increase blood clotting. Microclots seem to be relatively common18 in patients with long COVID and may contribute to circulation issues and many long COVID symptoms19, says Pollack.

Researchers hope to explore these and many other theories, including microbiome dysbiosis (or abnormal changes in bacteria), which seems more common in people with long COVID20 and endometriosis21.

For now, they say we need to keep digging. “People really have a tendency to think they see a pattern and then make everything fit the pattern they think they see,” says Male. That’s where research plays a crucial role: It offers subjective facts that help prove—or debunk—these explanations. And, once the truth is uncovered, it could eventually lead to improved treatments.

Where do we go from here?

Long COVID isn’t going away anytime soon, and it affects a lot of people. Getting to the bottom of exactly how it’s linked to reproductive health, including why symptoms tend to flare around a person’s period, can lead to better treatments for people who deal with these mysterious fluctuations every month.  “That’s actually my main driving goal,” Male says.

What’s more, if long COVID turns out to affect fertility or menstrual cycles, it could influence how people plan their families and seek fertility counseling, Male adds.

Doctors already have some effective treatment options. Azola says hormone replacement therapy often helps patients with early perimenopausal symptoms, for example. For those whose long COVID symptoms flare during their periods, taking a hormonal contraceptive and skipping the placebo week—which suppresses ovulation and evens out hormone fluctuations—may be a solution, say Azola and Male.

Because it can take time (and potentially many doctors) to get a diagnosis for long COVID, you have to be your own advocate, Azola says. Find a provider who seems open and listens to you, and be ready to potentially educate your doctor by sharing the latest research. “Most clinicians in general are curious and want to help people,” she says.

Most importantly, believe what your body is telling you. “You are not supposed to feel debilitating pain in your period. Sometimes I think that we just lose perspective of what is normal,” Soares says. “Considering the history of research in reproductive health for women and nonbinary people,” or, more accurately, the lack thereof, “I think we have to fight for recognition that we have an issue that is urgent and worth investigating.”

—medically reviewed by Andrea Braden, MD


Well+Good articles reference scientific, reliable, recent, robust studies to back up the information we share. You can trust us along your wellness journey.

  1. Pollack B, von Saltza E, McCorkell L, Santos L, Hultman A, Cohen AK, Soares L. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Front Rehabil Sci. 2023 Apr 28;4:1122673. doi: 10.3389/fresc.2023.1122673. PMID: 37234076; PMCID: PMC10208411.
  2. Edelman A, Boniface ER, Male V, Cameron ST, Benhar E, Han L, Matteson KA, Van Lamsweerde A, Pearson JT, Darney BG. Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data. BMJ Med. 2022;1(1):e000297. doi: 10.1136/bmjmed-2022-000297. Epub 2022 Sep 27. PMID: 36381261; PMCID: PMC9665108.
  3. Perlis RH, Santillana M, Ognyanova K, Safarpour A, Lunz Trujillo K, Simonson MD, Green J, Quintana A, Druckman J, Baum MA, Lazer D. Prevalence and Correlates of Long COVID Symptoms Among US Adults. JAMA Netw Open. 2022 Oct 3;5(10):e2238804. doi: 10.1001/jamanetworkopen.2022.38804. PMID: 36301542; PMCID: PMC9614581.
  4. Sigfrid L, Drake TM, Pauley E, Jesudason EC, Olliaro P, Lim WS, Gillesen A, Berry C, Lowe DJ, McPeake J, Lone N, Munblit D, Cevik M, Casey A, Bannister P, Russell CD, Goodwin L, Ho A, Turtle L, O’Hara ME, Hastie C, Donohue C, Spencer RG, Donegan C, Gummery A, Harrison J, Hardwick HE, Hastie CE, Carson G, Merson L, Baillie JK, Openshaw P, Harrison EM, Docherty AB, Semple MG, Scott JT; ISARIC4C investigators. Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol. Lancet Reg Health Eur. 2021 Sep;8:100186. doi: 10.1016/j.lanepe.2021.100186. Epub 2021 Aug 6. PMID: 34386785; PMCID: PMC8343377.
  5. Stewart S, Newson L, Briggs TA, Grammatopoulos D, Young L, Gill P. Long COVID risk – a signal to address sex hormones and women’s health. Lancet Reg Health Eur. 2021 Dec;11:100242. doi: 10.1016/j.lanepe.2021.100242. Epub 2021 Nov 2. PMID: 34746909; PMCID: PMC8561426.
  6. Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re’em Y, Redfield S, Austin JP, Akrami A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021 Aug;38:101019. doi: 10.1016/j.eclinm.2021.101019. Epub 2021 Jul 15. PMID: 34308300; PMCID: PMC8280690.
  7. Al-Najjar MAA, Al-Alwany RR, Al-Rshoud FM, Abu-Farha RK, Zawiah M. Menstrual changes following COVID-19 infection: A cross-sectional study from Jordan and Iraq. PLoS One. 2022 Jun 29;17(6):e0270537. doi: 10.1371/journal.pone.0270537. PMID: 35767537; PMCID: PMC9242447.
  8. Herrero Y, Pascuali N, Velázquez C, Oubiña G, Hauk V, de Zúñiga I, Peña MG, Martínez G, Lavolpe M, Veiga F, Neuspiller F, Abramovich D, Scotti L, Parborell F. SARS-CoV-2 infection negatively affects ovarian function in ART patients. Biochim Biophys Acta Mol Basis Dis. 2022 Jan 1;1868(1):166295. doi: 10.1016/j.bbadis.2021.166295. Epub 2021 Oct 27. PMID: 34718118; PMCID: PMC8550892.
  9. Wilkins J, Al-Inizi S. Premature ovarian insufficiency secondary to COVID-19 infection: An original case report. Int J Gynaecol Obstet. 2021 Jul;154(1):179-180. doi: 10.1002/ijgo.13719. Epub 2021 May 13. PMID: 33896002; PMCID: PMC9087667.
  10. Puca E, Puca E. Premature Ovarian Failure Related to SARS-CoV-2 Infection. J Med Cases. 2022 Apr;13(4):155-158. doi: 10.14740/jmc3791. Epub 2022 Mar 25. PMID: 35464328; PMCID: PMC8993449.
  11. Breintoft K, Pinnerup R, Henriksen TB, Rytter D, Uldbjerg N, Forman A, Arendt LH. Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Feb 9;10(4):667. doi: 10.3390/jcm10040667. PMID: 33572322; PMCID: PMC7916165.
  12. Wang S, Farland LV, Gaskins AJ, Mortazavi J, Wang YX, Tamimi RM, Rich-Edwards JW, Zhang D, Terry KL, Chavarro JE, Missmer SA. Association of laparoscopically-confirmed endometriosis with long COVID-19: a prospective cohort study. Am J Obstet Gynecol. 2023 Jun;228(6):714.e1-714.e13. doi: 10.1016/j.ajog.2023.03.030. Epub 2023 Mar 25. PMID: 36972892; PMCID: PMC10101545.
  13. Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med. 2022 Aug;28(8):1706-1714. doi: 10.1038/s41591-022-01909-w. Epub 2022 Jul 25. PMID: 35879616; PMCID: PMC9388369.
  14. Lim SH, Ju HJ, Han JH, Lee JH, Lee WS, Bae JM, Lee S. Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19. JAMA Netw Open. 2023 Oct 2;6(10):e2336120. doi: 10.1001/jamanetworkopen.2023.36120. PMID: 37801317; PMCID: PMC10559181.
  15. Sharma C, Bayry J. High risk of autoimmune diseases after COVID-19. Nat Rev Rheumatol. 2023 Jul;19(7):399-400. doi: 10.1038/s41584-023-00964-y. PMID: 37046064; PMCID: PMC10096101.
  16. Venkatesan P. Bacterial infection linked to endometriosis. Lancet Microbe. 2023 Oct;4(10):e768. doi: 10.1016/S2666-5247(23)00221-5. Epub 2023 Jul 18. PMID: 37478882.
  17. Swanepoel AC, Visagie A, de Lange Z, Emmerson O, Nielsen VG, Pretorius E. The clinical relevance of altered fibrinogen packaging in the presence of 17β-estradiol and progesterone. Thromb Res. 2016 Oct;146:23-34. doi: 10.1016/j.thromres.2016.08.022. Epub 2016 Aug 21. PMID: 27566845.
  18. Pretorius E, Vlok M, Venter C, Bezuidenhout JA, Laubscher GJ, Steenkamp J, Kell DB. Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc Diabetol. 2021 Aug 23;20(1):172. doi: 10.1186/s12933-021-01359-7. PMID: 34425843; PMCID: PMC8381139.
  19. Pretorius E, Venter C, Laubscher GJ, Kotze MJ, Oladejo SO, Watson LR, Rajaratnam K, Watson BW, Kell DB. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovasc Diabetol. 2022 Aug 6;21(1):148. doi: 10.1186/s12933-022-01579-5. PMID: 35933347; PMCID: PMC9356426.
  20. Hrncir T. Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms. 2022 Mar 7;10(3):578. doi: 10.3390/microorganisms10030578. PMID: 35336153; PMCID: PMC8954387.
  21. Zizolfi B, Foreste V, Gallo A, Martone S, Giampaolino P, Di Spiezio Sardo A. Endometriosis and dysbiosis: State of art. Front Endocrinol (Lausanne). 2023 Feb 20;14:1140774. doi: 10.3389/fendo.2023.1140774. PMID: 36891056; PMCID: PMC9986482.


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