1CIShci

FEATURE
HORMONES THROUGH HISTORY
MILESTONES
IN THE HISTORY OF HRT
WRITTEN BY SAFFRON WHITEHEAD
The story of hormone
replacement therapy (HRT)
begins in 1889 when, at the
age of 72, Charles Edouard
Brown-Séquard reported
to the Sociéte de Biologie
in Paris the invigorating
effects of injecting himself
eight times with an
aquaeous extract of dogs’
testicles. He attributed
this effect to an action on
the nervous system and
suggested that similar
extracts could be used to
rejuvenate men.
A few weeks later, the British Medical
Journal published an editorial entitled
‘The pentacle of rejuvenescence’,
indicating the unsettling nature of
these claims. Britain viewed Brown-
Séquard’s results with caution, whilst
Americans referred to it as ‘the elixir
of life’.
Charles Edouard Brown-Séquard
A year later, Brown-Séquard reported
©Wellcome Images, London
that an American woman, Augusta
Brown, had injected several women
with filtered juice of guinea pigs’ ovaries, so benefiting hysteria, uterine
afflictions and ageing debility. This claim could not be validated, but
in 1896 the first of several papers about the successful use of ovarian
extracts in the Landau Clinic in Berlin was published.
extracts could have striking effects
on the uterus when tested in the
laboratory. Soon the practice of
organotherapy came under attack by
scientists.
DISCOVERY OF
OESTROGENS
In 1923 Edgar Allen and Edward
Doisy partially purified an oestrogenic
hormone from pigs’ follicular fluid,
and in 1927 Bernhard Aschiem and
Selmar Zondek discovered that the
urine of pregnant women contained
a highly oestrogenic substance. This
led to the isolation of pure crystalline
oestrone by Doisy and colleagues in
1929, followed by progesterone in 1934,
oestradiol in 1935 and testosterone in
1939. In 1930, Zondek showed that
oestrogens could be produced from
pregnant mares’ urine.
These water-soluble oestrogens were
subsequently found to be conjugated
with acid or sulphate, and extracts
of these conjugated oestrogens were
put on the market as orally active
oestrogen preparations. In 1938,
ethinyl oestradiol was synthesised
and the first potent synthetic steroid,
diethylstilboestrol, was discovered –
both are long acting and highly active
oestrogens.
THE ERA OF ORGANOTHERAPY
Brown-Séquard’s naïve experiment led to the era of organotherapy, in
which a plethora of animal extracts, including glands, were used as
therapeutic agents. Organotherapy remained a contentious issue for
over 30 years, although it did reach some degree of respectability in
1891 after George Redmayne Murray’s success in treating myxoedema
(hypothyroidism) with extracts of thyroid glands.
The pharmaceutical companies had been quick to jump on the
organotherapy bandwagon and this included production of a
wide range of watery ovarian extracts, such as ‘ovarine oophorin’,
with dubious, if any, biological activity. It was not until 1912 that it
was discovered that the ‘active principle’ in the ovaries could only
be extracted using lipid solvents. Unlike watery extracts, the lipid
‘Progynon’ was a ‘hormone supplement’ used to treat the effects of the
female menopause. It first appeared on the market in Germany in 1928.
To make the pills more affordable, the hormone extract was obtained
from the urine of pregnant women.
©Science Museum London, Wellcome Images
20 | THE ENDOCRINOLOGIST | SPRING 2015