Hormonal stratification of COVID-19 risk categories
Women exhibit highly dynamic oestrogen trajectories across their
lifespan, from the initial pre-pubertal surge, to the regular cyclical
fluctuations with menstruation, the substantive increases with pregnancy
followed by post-partum resolution, and then the dramatic declines
observed with the onset of menopause or in the pathogenic state of
premature ovarian insufficiency. The scale of these changes is immense,
with pregnancy oestradiol levels frequently exceeding 1,000pg/ml as
compared to 30 to 400pg/ml for ovulating premenopausal women, and almost
undetectable levels in post-menopausal women. Progesterone levels
exhibit a 10-fold increase in across the menstrual cycle with formation
of the corpus luteum, with a further 10-fold increase during pregnancy,
before becoming negligible in the menopause. Female androgen
concentrations decline with age, to levels that approximate 50% of peak
values, however, even when testosterone is pathologically raised in
polycystic ovarian syndrome the values are still a fraction
(~1/20th) of that observed in males.
Notably these hormonal fluctuations underpin stratification of risk for
a range of diseases including hormonally sensitive cancers,
cardiovascular disease and thromboembolic disease.
Whether these marked changes in sex steroids underlie some of the
differences observed for disease progression for different female
populations is an area for further study6. The
relative low impact of SARS-Cov-2 on pregnant women may reflect their
relative shielding, or the pregnancy specific sex-steroid mediated
differential immune response. The increased incidence of complications
post-partum period may reflect resolution of physiological adaption to
pregnancy or hormonal changes but recording gestational age or time from
delivery is a prerequisite to understand disease course. For the
non-pregnant population epidemiological studies should record the
contraceptive methods being used and menstrual cycle characteristics, as
oestrogen containing oral contraceptive pills, progesterone only pills
and implants all frequently stabilise oestrogen levels removing
ovulatory fluctuations and early follicular troughs but with differing
efficacy. For older women where disease severity is increased,
clarification of the independent effect of the menopausal transition on
disease progression would be useful as age and reproductive stage may be
independent variables in determining disease
severity7. Whether exogenous hormone replacement
therapy is being taken, and if single or combined preparations and dose
may be central to help clarify if oestrogen supplementation mitigates
risk. Selective oestrogen receptor modulators like tamoxifen, which may
increase circulating oestradiol levels with prolonged use, also need to
be recorded.