29 Sept 2023 Episode 351 Episode 351: Vaginal bleedings and menstrual disturbances in relation to COVID infection and vaccines

Dear colleagues,

This week my curiosity was triggered by a short paper in Nature Briefing (Ep 351-1), asking attention for vaginal bleedings after COVID vaccination in non-menstruating women (either peri/post-menopausal or on contraceptives). These observations are of obvious concern, because this type of bleedings could otherwise be related to (pre-) cancerous  endometrial lesions and even, if “innocent” (self-limiting and reversible), they could lower vaccine acceptability in women and somehow feed the fake new that COVID vaccines interfere with fertility.   Therefore, I was wondering how solid and reproducible these data are and what could be the mechanisms.

Ep 351-2: Kristin Blix Sc Adv 2023 is the first study quoted in the Nature Briefing paper. It is about a Norwegian cohort with over 21,000 women, equally divided in post-menopausal, peri-menopausal, peri-menopausal women and pre-menopausal on contraceptives.

Among post-, peri-, and premenopausal women, 3.3, 14.1, and 13.1% reported having one or several unexpected vaginal bleeding episodes during the last 8 to 9 months, of which approximately 50% were reported to have happened within 28 days of mRNA vaccination. The latter corresponds to a clear 3 to 5 fold increase as compared to expected.   

Spikevax (Moderna) showed a 32 % higher risk in pre-menopausal women as compared to Comirnaty (Pfizer)

Ep 351-2: Katerine Lee Sc Adv 2022 is the second quoted reference in a “convenience” heterogenous sample of menstruating and non-menstruating women in the US

Dx =diagnose of reproductive condition; LARC = long-acting reversible contraceptives.

1. People with regular menstrual cycles: 42 % bled more heavily than usual
2. Non-menstruating people reporting breakthrough bleedings

• 71% of people on long-acting reversible contraceptives,
• 39% of people on gender-affirming hormones, and
• 66% of postmenopausal people

1. Factors associated with heavy bleedings in menstruating women

2. Factors associated with breakthrough bleedings

THUS: Risk factors = age, systemic vaccine side effects (fever and/or fatigue), history of pregnancy or birth, and ethnicity.

Ep 351-4: Vojka Lebar J Clin Med 2021: Review on effect of COVID infection on menstrual cycle

Consequence of SARS-CoV-2: decrease  menstrual volume and a prolongation of the menstrual cycle.

Severity COVID-19 does not play a role in menstrual cycle changes.

Ep 351-5: Gall Isakov Reproduct. Sc 2023: online nationwide questionnaire on premenopausal,

non-pregnant women over 18 years of age in Israel, querying about any changes in their menstrual patterns after COVID-19 infection or vaccination (Pfizer).

Risk factors:

• Increasing age.
• Baseline menstrual pattern of prolonged, frequent, and heavy menses
• Greater use of non-hormonal IUD

Ep 351-6: Al Kahdri J Infect Pub Health 2023: Meta-analysis of abnormalities in cycle after COVID vaccination: increase in menorrhagia (abundant menses) + 25%;

oligomenorrhea (inconsistent and infrequent menses) + 22 %

and polymenorrhea (too frequent menses): + 16 %

with large differences between studies

1. Menorrhagia

2. Oligomenorrhea

3. Polymenorrhea

Ep 351-7: Rickard Ljung BMJ March 2023: Cohort of almost 3 million Swedish healthy women (no menstruation disorders or cancer history) age 12-74: after COVID vaccination or infection. 

Outcome: health care contacts for menstrual disturbance

• Premenopausal: no increased risk
• Postmenopausal: very weak association, but inconsistent.
• Also no clear association with menstrual disturbance after SARS-CoV-2 infection

Note: Studies that found association were usually based on self-reporting via (online) questionnaires.

Ep 351-8: Angela Taylor BMJ Editorial comment on Ljung paper (Ep 351-7)

• Any postmenopausal bleeding truly related to vaccination is likely benign
• However: the association between vaccination and bleeding appears to be weak
• In general: approx. 9 % of cases of postmenopausal bleeding is a sign of endometrial cancer

Therefore: Postmenopausal bleeding must be investigated, even when it follows vaccination.

MY PROVISIONAL CONCLUSION:

There is some evidence of menstrual disturbance, related to COVID infection, but it is certainly not very severe.

There are many papers suggesting increased incidence of vaginal bleedings and possibly other disturbances in both pre- and postmenopausal women after vaccination.

In most instances, these bleedings/disturbances are based on self-reporting and are also self-limiting.

The biggest Swedish study, based on a more objective analysis of medical contacts in 3 million women shows no convincing association with health care seeking for bleeding after infection or vaccination.

These data are rather reassuring, since at first view, COVID disease or vaccination does not seem to lead to serious or persistent menstrual disturbance or breakthrough bleedings.

Clearly, in post-menopausal women, vaginal bleeding (whether in the context of COVID vaccination or not) should call for medical attention to exclude unrelated pathology (e.g. cancer).

Best wishes,

Guido