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HORMONES THROUGH HISTORY
FEATURE
TABLE 1. FINDINGS OF THE WOMEN’S HEALTH INITIATIVE AND MILLION WOMEN STUDY
OESTROGEN PLUS PROGESTERONE
Risk of:
breast cancer
stroke
blood clots
?
Effects on:
breast cancer
OESTROGEN ALONE
=
Risk of:
bowel cancer
Risk of:
bowel cancer
osteoporosis
Risk of:
stroke
blood clots
Risk of:
fractures
THE RISE OF MENOPAUSAL OESTROGEN THERAPY
Initially, oral and injectable oestrogens were marketed for the treatment
of menstrual irregularities. However, by the early 1930s, reports of
their use for treating menopausal symptoms began to appear. The
index for their success was evaluated in terms of the reduction of hot
flushes rather than other associated symptoms of the climacteric. By
the end of the 1930s, the American gynaecologist Emil Novak wrote
‘…the efficacy of oestrogenic therapy is clearly to be explained by the
undoubted physiological potency of these preparations… Contrast
this with the uncertainty of ovarian therapy before the isolation of the
oestrogenic hormone’.
The UK lagged behind America in prescribing oestrogen replacement
therapy, but opening menopause clinics helped to raise the profile of
the menopause amongst non-specialist GPs and women. Widespread
publicity was driven by the publication of Robert Wilson’s popular and
polemic book, Feminine Forever in 1966.
This American gynaecologist argued that menopausal women were
castrates suffering from a deficiency disease; ‘The transformation
within a few years of a formerly pleasant energetic woman into a dullminded
but sharp-tongued caricature of her former self is one of the
saddest of human spectacles.’ He argued that all women should take
oestrogen therapy to keep them young and sexually active. The book
sold 100,000 copies within 7 months of publication.
Widespread publicity in the UK was to come later, and has often been
attributed to Wendy Cooper’s journalistic profile and publication of her
book No Change in 1975.
HRT CONTROVERSIES
This was the same year that the rumbling controversy over oestrogens
and risks of breast and uterine cancer erupted. Donald Smith and
colleagues published the first epidemiological evidence of an increased
risk of carcinoma amongst oestrogen users. By 1980, 14 studies on
oestrogen replacement therapy and endometrial cancer had been
published, seven in New England Journal of Medicine.
Prescriptions of oestrogen therapy dropped dramatically and so
pharmaceutical companies promoted the use of combined oestrogen/
progestagen preparations to induce a bleed and reduce risks of uterine
hyperplasia. The combined hormone preparations became generally
known as HRT. Edmund Novak (Emil’s son, also a gynaecologist)
stated, ‘What 60-year-old woman needs continued menstruation as a
badge of femininity?’
The second response of the pharmaceutical companies was to promote
extended use of HRT for the prevention of osteoporosis (in particular)
and cardiovascular disease, but not all doctors agreed with its long
term use.
The prescribing of HRT saw a further major setback in the early 2000s
after the publication of research from the USA’s Women’s Health
Initiative (WHI) and the UK’s Million Women Study (MWS), reporting
observed risks and benefits of HRT (summarised in Table 1). There
was widespread coverage in the press. A quote from The Observer in
2002 summed it up in a nutshell: ‘Damning study on HRT leaves
women in limbo. The startling news that HRT may do more harm
than good has caused worldwide confusion and panic. Where do the
answers lie?’
Prescriptions of HRT dropped by up to 50% in some countries. Results
of the studies were subsequently reanalysed and concerns about their
conclusions arose. By 2011, the fourth MWS report concluded that the
risk of breast cancer reverts to levels of non-users 2 years after stopping
HRT. Today, long-term hormone replacement therapy is no longer
advised and should only be used to treat menopausal symptoms, not
for any extended health benefits it may have.
So no longer ‘feminine forever’ or do our social constructs and increasing
longevity in the Western world now allow oestrogen deprived postmenopausal
women to live healthy and normal lives without HRT?
Meanwhile we remain in limbo, and the rocky road of the history of
HRT continues.
SAFFRON WHITEHEAD
Emeritus Professor of Endocrine Physiology,
St George’s University of London
THE ENDOCRINOLOGIST | SPRING 2015 | 21