COVID-19 Pandemic Stress Affected Ovulation, Not Menstruation

Disruptions in ovulation that caused no real changes in women’s menstrual cycles were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of a “nature experiment” that made it possible. for comparison with women a decade earlier.

Findings from two studies of women of reproductive age, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at ENDO 2022: The Endocrine Society Annual Meeting.

The comparison of the two periods produced several new findings. “I was taught in medical school that when women don’t eat enough, they lose their periods. But what we now understand is that there is a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disorders, some of which are subclinical or not obvious,” said Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver, Canada.

In addition, women’s menstrual cycle lengths did not differ across the two periods, despite a dramatic 63% decline in normal ovulatory function associated with increased depression, anxiety, and external stress that the women reported in diaries.

“Assuming that regular cycles require normal ovulation is something we just have to get out of our minds. It changes our concept of what is normal if we just know about the cycle length,” she observed.

It will be critical in the future to see if the ovulatory disturbances have resolved as the pandemic has shifted “because there is strong evidence that ovulatory disturbances, even with normal cycle length, are associated with bone loss and some evidence that they are associated with early heart attacks, breast and endometrial cancers,” Prior said at a press conference.

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, said Medscape Medical News: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then impacts ovulatory function.”

Neal-Perry noted that the association of stress and ovulatory disruption has been previously reported in various ways, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There are a few studies that show a genetic predisposition and a genetic disorder that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me, one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you if there have been changes. We know that weight gain or weight loss can stress the reproductive axis,” Neal noted. -Parry of the Department of Obstetrics and Gynecology at the University of North Carolina School of Medicine, Chapel Hill.

Experiment of nature Revealing invisible effect of pandemic stress

The women in both cohorts of the Menstrual Ovulation Study (MOS) were healthy volunteers aged 19–35 years recruited from the metropolitan Vancouver region. All menstruated monthly and none took hormonal birth control. Recruitment for the second cohort began just prior to the March 2020 COVID-19 pandemic shutdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both had an average age of about 29 years and a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the previous one and more in line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs 80.4%; P = .002).

The distribution of menstrual cycle lengths did not differ, with both cohorts averaging approximately 30 days (P = .893). Although 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disorders,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier group, “which is remarkable, actually incredible,” Prior noted. .

The difference was also not explained by any of the demographic information collected, including socioeconomic status, lifestyle, or reproductive history variables.

And this was not due to COVID-19 vaccination, as the vaccine was not available when most of the women were recruited, and of the 79 recruited during vaccine availability, only two had a COVID- 19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities and worry are likely causes

The information from the diaries was more revealing. Several diary components were much more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stress), self-esteem, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disorders.

“So menstrual cycle lengths and long cycles did not differ, but there was a much higher incidence of silent or subclinical ovulatory disorders, and this was related to the increased stress that women recorded in their diaries. This means that the estrogen levels were reasonable close to normal, but the progesterone levels have decreased remarkably,” Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“This is a new observation because previously we’ve always thought that you need to ovulate to even have cramps,” she said.

When asked if COVID-19 itself may have played a role, Prior said no woman in the study tested positive for the virus or had COVID for a long time.

“As far as I’m aware, it was the changes in employment … and caring for the elderly and worrying about illness in someone you loved that was related,” she said.

Asked what she thought the result would be if the study was done now, she said: “I don’t know. We’re still in a stressful time with inflation and not fully recovered, so probably the issue is still very much present .”

Prior and Neal-Perry have not reported any relevant financial relationships.

ENDO 2022. Offered June 12, 2022.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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