Clinical practice: guidelines, position statements, recommendations and tool kits

EDITOR-IN-CHIEF

Although Aristotle is said to have described women’s post-reproductive health thousands of years ago, improvements in our understanding and delivery of midlife health care for women changed very little until the early twentieth century.

The physiological studies by William Maddock Bayliss and Ernest Henry Starling, at the beginning of the last century, demonstrated the existence of specific messenger molecules (subsequently called hormones) circulating in the blood that regulate organ function and physiological mechanisms [1]. These findings led to the concept and specialty of endocrinology. The first two hormones – secretin, discovered in 1902, and gastrin, discovered in 1905 – both arose from the gut.

Many others were to follow – notably, for those of us concerned with the reproductive health of women, the ovarian hormones estrogen, progesterone and testosterone. Isolation of these hormones and descriptions of their chemical structure followed, as did an understanding of the feedback control mechanism, existing between the hypothalamus, pituitary and ovary, so critical to women’s reproductive health.

This was a fertile time for reproductive endocrinologists.

Interest in in vitro fertilization, initially in animals, had existed for centuries but scientific, technical and ethical challenges meant that it was not until the mid-twentieth century that research in humans progressed and ultimately led to the first live birth of an in vitro fertilization-conceived baby in 1978 [2]. Since that time, many millions of children have been born following conception via in vitro fertilization [3]. Data have been accumulated on long-term outcomes and the procedures used have been evaluated and adapted based largely on solid evidence. Today, all aspects of assisted reproduction are governed by strict ethical and clinical protocols.

Meanwhile, research into the treatment of postmenopausal women was hampered by a lack of understanding of the cause of symptoms. In 1886 two German studies reported on the use of bovine ovarian tissue, from reproductive-age cows, in the treatment of menopausal symptoms. In 1889 Charles Brown-Sequard, sometimes referred to as ‘The Father of Endocrinology’, injected himself with an extract of guinea pig and dog testicles which he claimed had ‘rejuvenated’ him. He suggested similar treatments may have the same effect on women [4]. Such a product was manufactured in the 1890s by Merck and Co. for treatment of symptoms of menopause. In 1993, in the USA, the first human estrogen product, Emmenin, was produced by Ayerst Laboratories from the urine of pregnant women, only to be replaced in 1941 by Premarin, a mixture of ‘conjugated estrogens’ derived from the urine of pregnant mares. The first affordable orally active estrogen preparation for the treatment of menopausal women had arrived.

Several publications espousing the benefits of hormone therapy for the treatment of ‘menopausal disorders’ followed, as did what might be described as the first ‘clinical guideline’ of the day, Robert Wilson’s book Feminine Forever. Use of menopausal hormone therapy (MHT) expanded rapidly and by 1975 conjugated estrogen was the fifth most prescribed drug in the USA [5].

The rise and rise of postmenopausal estrogen therapy is an all too often repeated example of clinical medicine rushing to embrace an effective product without pausing to consider adverse effects. Use of MHT was mostly influenced by industry marketing, either direct to the consumer or to clinicians.

Many women benefited and additional skeletal and cardiovascular benefits were identified but, as we all know, unexpected harms including an increase in thromboembolic disease and endometrial and breast cancer were subsequently detected. The release of data from The Women’s Health Initiative (WHI) trials in 2002 [6], and subsequently, not only halted the growing use of MHT but led to an over-correction by clinicians with drastic curtailment of use globally.

Suddenly, it seemed, prescribing hormones to perimenopausal and postmenopausal women had become controversial and guidelines were needed.

The North American Menopause Society released guidelines on the use of MHT [7] almost immediately after the release of WHI data, followed shortly after by Recommendations from the International Menopause Society [8]. These societies and many others have continued to update their guidelines, recommendations and position statements ever since.

Usually, the result has been longer, more detailed documents aimed at covering every nuance of the subject. Many are excellent reference documents but not much help at the clinical coal face.

In 2014 this journal published ‘A Practitioner’s Toolkit for Managing Menopause’ [9]. This document used clinical experience in primary care combined with published diagnostic algorithms, position statements from learned medical societies and relevant peer-reviewed literature to develop assessment and management algorithms relevant to the primary care of women aged 40 years and older. The result was an accessible desktop tool for health-care practitioners caring for women at midlife. The document has been viewed 42,445 times since, a testament to its clinical applicability.

This issue of Climacteric contains a completely revised 2023 version of the Practitioner’s Toolkit for Managing Menopause [10]. This clinical aid has been informed by a systematic search for guidelines, position statements and consensus statements pertaining to menopause published after 2014. Key recommendations from those clinical practice guidelines determined to be the most robust were included and peer-reviewed literature was searched for any information gaps, including information on new therapies, to update the assessment and management algorithms within the Toolkit.

I commend it to you.