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SPECIAL REPORT

Managing Menopausal Symptoms and the role of Hormone Replacement Therapy

Glands and Hormones - the Testes, Ovaries, the Menopause, Cancer and Weak Bones The Skin as a Mechanism to Deliver Hormone Replacement Therapy (HRT) and as a Beneficiary The Diagnosis of Menopause and Perimenopause and Choosing the Right ‘Cocktail’ of Treatment Vasomotor Symptoms, the Diagnostic Pathway, Life Style Changes, Mental Health, Sexual Pleasure and the Menopause

Published by Global Business Media


MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

SPECIAL REPORT

Managing Menopausal Symptoms and the role of Hormone Replacement Therapy

Contents Foreword

3

Dr Charles Easmon, Editor

Glands and Hormones - the Testes, Ovaries, the Menopause, Cancer and Weak Bones The Skin as a Mechanism to Deliver Hormone Replacement Therapy (HRT) and as a Beneficiary The Diagnosis of Menopause and Perimenopause and Choosing the Right ‘Cocktail’ of Treatment Vasomotor Symptoms, the Diagnostic Pathway, Life Style Changes, Mental Health, Sexual Pleasure and the Menopause

Published by Global Business Media

Published by Global Business Media Global Business Media Limited 62 The Street Ashtead Surrey KT21 1AT United Kingdom

Glands and Hormones – the Testes, Ovaries, the Menopause, Cancer and Weak Bones

4

Joanna Fischer, Medical Correspondent

The Testes The Ovaries What Makes a Man a Man and a Woman a Woman? Transgender and Non-‘Binary’ The Menopause Cancer, Weak Bones and the Menopause Summary

Switchboard: +44 (0)1737 850 939 Fax: +44 (0)1737 851 952 Email: info@globalbusinessmedia.org Website: www.globalbusinessmedia.org

The Skin as a Mechanism to Deliver Hormone 7 Replacement Therapy (HRT) and as a Beneficiary

Publisher Kevin Bell Business Development Director Marie-Anne Brooks

The Skin as a Safe Vehicle for Hormone Replacement Therapy Perfect Skin Summary

Editor Dr Charles Easmon MBBS MRCP MSc Public Health DTM&H DOccMed

The Diagnosis of Menopause and Perimenopause and Choosing the Right ‘Cocktail’ of Treatment

Senior Project Manager Steve Banks

Joanna Fischer, Medical Correspondent

Advertising Executives Michael McCarthy Abigail Coombes Production Manager Paul Davies For further information visit: www.globalbusinessmedia.org

The opinions and views expressed in the editorial content in this publication are those of the authors alone and do not necessarily represent the views of any organisation with which they may be associated. Material in advertisements and promotional features may be considered to represent the views of the advertisers and promoters. The views and opinions expressed in this publication do not necessarily express the views of the Publishers or the Editor. While every care has been taken in the preparation of this publication, neither the Publishers nor the Editor are responsible for such opinions and views or for any inaccuracies in the articles. © 2017. The entire contents of this publication are protected by copyright. Full details are available from the Publishers. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical photocopying, recording or otherwise, without the prior permission of the copyright owner.

Dr Charles Easmon, Editor

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Premature Ovarian Insufficiency Bio-Identical versus Body-Identical Hormone Replacement Therapy The Wise Woman’s Dilemma Types of HRT – Different Oestrogens and Progestogens A Womb of One’s Own Summary

Vasomotor Symptoms, the Diagnostic Pathway, Life Style Changes, Mental Health, Sexual Pleasure and the Menopause Dr Charles Easmon, Editor

The Ideal GP Menopause Consultation (Based on NICE Guidelines) Things to Avoid in the Menopause Complimentary Medicines Mental Health, Sexual Pleasure and the Menopause Summary

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

Foreword T

he job of a messenger is to get a message

of progesterone and oestrogen, women can expect

from point A to point B in the most effective

to feel more tired, gain weight, suffer mood swings,

way possible with minimal damage to the content

depression and anxiety etc. Follow the National

and the ‘carrier’ as possible. Skin is an effective

Institute for Health and Care Excellence (NICE)

and safe way of getting hormone replacement into

Guidance based on the symptoms of any women

the female body.

aged 452 or over without the need for inconclusive

Hormones are messengers. They are mainly

blood tests etc.

secreted from glands. If all our glands were collected,

Despite seeing the value of HRT, we must also ask

bagged up and thrown away we would be talking

is it safe3 and, if not, what should we do? As clinicians,

of a small bag weighing under a kilogram, but the

we are used to asking personal and family history and

effect would be devastating to our functioning and

for HRT this is itself our risk assessment. If the woman

quality of life in ways predictable and unpredictable.

has a clear history of breast cancer4 or a family history

As they age, women have a significant reduction

of blood clots, then HRT’s risk/benefit analysis is not

in their oestrogen and progesterone levels and the

likely to be favourable, and if surgery is required whilst

debate will always rage about does this matter and if

on HRT, it must be considered as a risk factor for

it’s a natural process why disrupt it? The best answer,

blood clots5. Skin based HRT reduces these risks.

backed up by hundreds of scientific studies, is to ask a woman who has had hormone replacement therapy how she felt before and after1. The answer is usually positive or very positive in that, without higher levels

Dr Charles Easmon Editor

Dr Charles Easmon is a medical doctor with 30 years’ experience in the public and private sectors. After qualifying as a physician, he developed his interests in occupational medicine, public health and travel diseases.

References: 1

https://www.nice.org.uk/guidance/ng23/chapter/Recommendations#individualised-care Accessed 11/6/17

2

https://www.nice.org.uk/guidance/qs143/chapter/Quality-statement-1-Diagnosing-perimenopause-and-menopause Accessed 11/6/17

3

https://www.nice.org.uk/news/press-and-media Accessed 11/6/17

4 5

http://bit.ly/2rNFrsz Accessed 11/6/17 https://www.nice.org.uk/guidance/cg92/chapter/1-Recommendations#assessing-the-risks-of-vte-and-bleeding-2 Accessed 11/6/17

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

Glands and Hormones the Testes, Ovaries, the Menopause, Cancer and Weak Bones Joanna Fischer, Medical Correspondent

Sexual identity can be regarded as an external set of values and behaviours, many of these culturally instituted (pink for girls and blue for boys)

The Testes Human life would end without testes (also true of course for the ovaries). There would be no sperm and no testosterone1. Testosterone is required for the proper physical development of boys and it is involved in the growth of facial and body hair, the lowering of the voice, increases in height and muscle mass as well as the growth of the Adam’s apple. In adults, the hormone maintains muscle strength, bone density and libido2. Interestingly men produce both oestrogen3 and progesterone4 but both in lower amounts than women. High levels of oestrogen are thought to correlate with prostatic enlargement. Debate about the existence or not of a ’male menopause’ will swing back and forth for many more years. However, it is clear that abnormally low levels of progesterone in men lead to symptoms that include mood swings, depression, insomnia, appetite changes, weight gain, irritability, migraines, anxiety, fatigue, and low sex drive. But this is not as frequent or as inevitable as the cliff-hanger that women face when their egg production stops.

The Ovaries The ovaries produce the female sex hormones that control reproduction. Their non-endocrine function is to produce the substrate (gametes) for the embryo. Oestrogen during puberty controls the development of the mammary glands and during the menstrual cycle stimulates the development of the uterine lining. Progesterone during pregnancy acts on the uterus to develop the womb5 and allow the implantation of the embryo. The pre-menopausal, post-pubertal monthly cycle of women changes over a typical 28-day cycle (range 21-35) affected by hormones from the anterior pituitary. The Follicle Stimulating Hormone (FSH) is self-explanatory; whereas the Luteinising Hormone (LH) stimulates ovarian follicles to produce oestrogen in the first half of 4 | WWW.PRIMARYCAREREPORTS.CO.UK

the cycle and then, after the egg is released, stimulates the remaining corpus luteum to produce progesterone6.

What Makes a Man a Man and a Woman a Woman – Transgender and Non-‘Binary’ For many years, we might have assumed that genitalia define us. However, an estimated 5% of children born every year are not clearly male or female (intersex7,8,9). Transgender issues have become more prominent with the successful Amazon series ‘Transparent10’ and Olympic athlete Bruce Jenner’s transformation to Caitlyn11, honoured by the front cover of Vanity Fair in 2015. Another Amazon series, “Orange is the New Black12”, has made a star out of a person, Asia Kate Dhillon13 who was born female but now identifies as neither gender (non-binary14). Australia now allows a passport entry that is neither male nor female15. The actress Emma Watson recently won the first non-gendered award16. There are challenges ahead for us and our children to understand and explain all this. Sexual identity can be regarded as an external set of values and behaviours, many of these culturally instituted (pink for girls and blue for boys). Genitalia are affected by hormones and can be manipulated alongside gender reassignment surgery to give a new phenotype. Our clichéd images of what makes a man a man and a woman a woman are being challenged, but the developmental general and life experiences of a transgender person prior to gender reassignment make this a complex subject with no easy answers. One thing we do know is that a person with no egg producing apparatus, by definition, will not experience the menopause.

The Menopause Men age and women age but for women the effect of hormone imbalance is symptomatically far greater. The menopause leads to symptoms in women aged 45 or older that include; hot


MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

Primary Care Reports

“Every woman’s experience of the menopause is different,” says Norma Goldman, founder and director of The Menopause Exchange17.

flushes, night sweats, infrequent or no periods, mood changes, memory or concentration loss, vaginal dryness, lack of interest in sex, joint and muscle stiffness and headaches18.

Cancer, Weak Bones and the Menopause A surprising national headline of 12 July 2017 stated that ‘Cancer is more common than marriage’. Marriage is on the decline but cancer is on the rise as we live longer. Women and men have to be concerned about bowel and lung cancer and both of these have modifiable risks in terms of smoking, alcohol, obesity and (red) meat-eating. Unique to women are breast, ovarian and endometrial cancers. Breast cancers are the easiest to screen for whether by women checking

their own breasts or by organised mammography programmes. Concerns were raised about whether hormone replacement therapy (HRT) would increase the risk of breast cancer and despite, lurid newspaper headlines, this is not a major risk for most women. Ovarian cancer is notoriously difficult to detect until it is too late. It is a classic anatomically ‘hidden’ cancer. New advances may help in the much earlier detection of this cancer. There is no direct link between ovarian cancer in terms of either menopause or HRT. Endometrial cancer is rarer than ovarian and is also a ‘hidden’ cancer. Interestingly research shows that HRT has a beneficial effect in reducing the incidence of endometrial cancer if the correct balance is given to women who still have a womb.

A review 3 months after starting a treatment for menopausal symptoms ensures that changes to dosage or formulation can be made if there are persistent side effects such as bloating, nausea and breast discomfort. Once treatment is established, further review is needed to assess new or pre-existing health problems, to carry out basic health checks (for example, measuring weight and blood pressure), and to inform and engage women in national screening programmes. Review should take place at least once a year, but may be needed more often if there are clinical indications for this. For most women, the symptoms of menopause respond well to treatment. However, for some whose symptoms do not improve or side effects are troublesome, review will identify if they need to be referred for help and support from a healthcare professional with specialist training and expertise19.

The specialist online research resource for General Practitioners and other senior primary care professionals Visit: www.primarycarereports.co.uk

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

It is clear that the societal and economic savings of the correct treatment are very significant indeed

However, these women must not be given just oestrogen (which alone would lead to the proliferation of endometrial tissue and increase the risk of endometrial cancer). Metastatic cancer can obviously affect bone but, almost as important, as women age is the risk of weaker bone via osteoporosis or osteopaenia. Fractures and associated disability or surgery with its possible complications are the consequences of women not having good ‘bone strength’. There is excellent evidence that HRT leads to increased bone preserving activity.

Summary Women with symptoms of menopause, whether caused by the normal natural process or those with iatrogenic menopause or premature ovarian failure should be offered HRT following NICE guidelines. The benefit to the women and to society is improved quality of life, less mental health issues, a reduced risk of endometrial cancer and a lesser burden of problems caused by both osteoporosis and osteopaenia. It is clear that the societal and economic savings of the correct treatment are very significant indeed. The National Institute for Health and Care and Excellence (NICE) gives clear advice about the use of HRT and when not to use it and advises on safe HRT regular review as below:

References:

http://www.healthline.com/human-body-maps/testis Accessed 7/6/17

1 2

https://www.endocrineweb.com/endocrinology/overview-testes Accessed 7/6/17.

http://www.ihealthdirectory.com/estrogen-men/ Accessed 11/6/17.

https://www.ncbi.nlm.nih.gov/pubmed/15669543 Accessed 11/6/17.

http://www.innerbody.com/image_endoov/repo07-new2.html#full-description Accessed 7/6/17

http://emedicine.medscape.com/article/1949171-overview Accessed 7/6/17

http://www.isna.org/faq/what_is_intersex Accessed 11/6/17.

3 4 5 6 7 8

https://medlineplus.gov/ency/article/001669.htm Accessed 11/6/17.

http://www.isna.org/faq/frequency Accessed 11/6/17.

9

http://www.imdb.com/title/tt3502262/ Accessed 11/6/17.

10

http://www.vanityfair.com/hollywood/2015/06/caitlyn-jenner-bruce-cover-annie-leibovitz Accessed 11/6/17.

11

http://www.imdb.com/title/tt2372162/ Accessed 11/6/17.

12

http://www.imdb.com/name/nm3545872/ Accessed 11/6/17.

13

http://www.tht.org.uk/sexual-health/Sex,-reproduction-and-gender/Trans-women/Nonbinary Accessed 11/6/17.

14

http://www.bbc.co.uk/news/world-asia-pacific-14926598 Accessed 11/6/17.

15

http://www.bbc.co.uk/newsbeat/article/39841483/emma-watson-wins-first-gender-neutral-mtv-tv--movie-award-for-beauty--the-beast Accessed 11/6/17.

16

17

http://www.menopause-exchange.co.uk/downloads/health-and-lifestyle-tips-for-the-menopause.pdf Accessed 7/6/17

https://www.nice.org.uk/guidance/qs143/chapter/Quality-statement-1-Diagnosing-perimenopause-and-menopause Accessed 11/6/17. 18

https://www.nice.org.uk/guidance/qs143/chapter/Quality-statement-4-Reviewing-treatments-for-menopausal-symptoms Accessed 11/6/17.

19

6 | WWW.PRIMARYCAREREPORTS.CO.UK


MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

The Skin as a Mechanism to Deliver Hormone Replacement Therapy (HRT) and as a Beneficiary

Primary Care Reports

Dr Charles Easmon, Editor

Women over 45 years presenting with menopausal symptoms are diagnosed with perimenopause or menopause based on their symptoms alone, without confirmatory laboratory tests1.

T

HE SKIN is the largest organ of the body2. In adults, it has a surface area (depending on size) of at least 2 square metres and, if fully laid out, might fill the space of a tiger skin and polar bear combined. It has layers including the outer epidermis, the dermis and the subcutaneous layer. It protects and nourishes and, of course, it needs to be protected and nourished itself. Archaeological digs of human and pre-human habitation seem to indicate that the use of balms, poultices and salves is very ancient3. From the earliest days, it has been known that therapy can be given through the skin4. In more recent times, great excitement and investment was put into a failed technological promise – vaccines via the skin. The company was called Powderject5 and the idea was that, via a series of pins on a patch attached to a gun applicator, the vaccine would be delivered into the skin and hence prevent

the need for a subcutaneous or intramuscular injection. Sadly, this did not work and the company got bought out. However, the skin as a delivery mechanism for substances other than vaccines is a well-studied and proven model of therapeutic drug delivery.

The Skin as a Safe Vehicle for HRT Adherence has been the buzzword in medicine over compliance for some years now. As a General Practitioner, you need your patients to willingly use your recommended therapies for their own benefit rather than feeling compelled to do so. For a woman to apply a medication to her skin, as part of her daily routine is easy and, studies show, has a higher uptake than the requirement for daily oral tablets. Skin-based HRT can also use lower doses of oestrogen and a special formulation of non-synthetic progesterone

The specialist online research resource for General Practitioners and other senior primary care professionals Visit: www.primarycarereports.co.uk

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

The skin is an excellent way for women to acquire their HRT on a daily basis. It is lower risk than oral HRT and has a higher chance of

(micronised6). The combined innovations in skinbased HRT have been shown to reduce the risk of side effects and complications from HRT such as venous thromboembolism7 (VTE) and cardiovascular complications.8 The National Institute for Health and Care Excellence (NICE) provides clear guidance on avoiding any harm from HRT.

1. Do not offer hormone replacement therapy (HRT) (including oestrogen/

continued adherence

progestogen combination) routinely to women with menopausal symptoms and a history of breast cancer. HRT may, in exceptional cases, be offered to women with severe menopausal symptoms and with whom the associated risks have been discussed9. 2. D  o not offer systemic hormone replacement therapy for the treatment of urinary incontinence10.

Most women want to look good and their skin looking good and healthy is part of that. Skin that reddens13 easily or oozes sweat (vasomotor effects) in social situations is obviously not helpful to confidence or sexual attraction. In most Western societies, hair in the right place adds to attractiveness and hair in the wrong place detracts. The menopausal woman not on HRT has a double whammy of thinning head hair and facial hirsutism (“even a single hair casts a shadow14,”), both of which fortunately are relieved by HRT. We all recognise the facial features of someone who feels sad (we still have one over the computers in this area). A chronically sad, anxious or depressed person has this ‘etched’ on their face in the form of lines or skin affected by poor lifestyle choices in terms of smoking, eating and drinking. The depressed woman is likely to take less care of her personal appearance and hence compounds a cycle of feeling unattractive. The role of HRT in mood alleviation should not be ignored, especially since the World Health Organisation (WHO) now recognises depression as the leading cause of disability15 worldwide.

Perfect Skin

Summary

Hard leathery or dry skin11 is aesthetically unpleasant and can be uncomfortable. The vagina is normally well lubricated for sexual activity but it can become dry and atrophic12 in the menopause which, in addition to the lack of sexual desire, can lead to uncomfortable and infrequent sex. This in itself has an impact on relationships.

The skin is an excellent way for women to acquire their HRT on a daily basis. It is lower risk than oral HRT and has a higher chance of continued adherence. The skin directly benefits from the HRT with a reduction in dryness, hot flushes, hirsutism and alopecia. More happiness and more confidence can be rubbed into the skin in an acceptable therapeutic solution.

HRT ‘may be beneficial in improving mood in early postmenopausal women with depressive and/or anxiety symptoms16.’

References:

1

h  ttps://www.nice.org.uk/guidance/qs143/chapter/Quality-statement-1-Diagnosing-perimenopause-and-menopause Accessed 11/6/17

2

http://www.nationalgeographic.com/science/health-and-human-body/human-body/skin/ Accessed 11/6/17

3

http://www.medicalnewstoday.com/info/medicine/prehistoric-medicine.php Accessed 11/6/17

4

http://www.bible-history.com/isbe/B/BALM/ Accessed 11/6/17

5

http://powerbase.info/index.php/PowderJect Accessed 11/6/17

6

https://www.sharecare.com/health/endocrine-system/what-is-micronized-natural-progesterone Accessed 11/6/17

7 8

8 | WWW.PRIMARYCAREREPORTS.CO.UK

http://www.bmj.com/content/336/7655/1227?tab=responses Accessed 11/6/17 http://bit.ly/2to2pZt Accessed 11/6/17

9

http://bit.ly/2rNFrsz Accessed 11/6/17

10

http://bit.ly/2svZpd6 Accessed 11/6/17

11

http://www.webmd.com/beauty/features/menopause-dry-skin-hormone-connection#1 Accessed 11/6/17

12

http://www.imsociety.org/manage/images/pdf/d0ad344b44faf5462478553de7000647.pdf Accessed 11/6/17

13

http://www.dermnetnz.org/topics/menopause-and-the-skin/ Accessed 11/6/17

14

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hirsutism/

Accessed 11/6/17

15

http://www.who.int/mediacentre/factsheets/fs369/en/ Accessed 11/6/17

16

http://www.imsociety.org/manage/images/pdf/ba6379e868044bec13015ac2b84f2753.pdf Accessed 11/6/17


MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

The Diagnosis of Menopause and Perimenopause and Choosing the Right ‘Cocktail’ of Treatment

Primary Care Reports

Joanna Fischer, Medical Correspondent

F

OR A diagnosis of menopause, the complete cessation of periods for 12 months whilst not on oral contraceptives is required. The time of irregular periods leading up to that can be called the perimenopause. The National Institute for Health and Care Excellence (NICE) are clear that no testing is required for the menopause and that the diagnosis is based on symptoms only, but for the perimenopause, Follicle stimulating Hormone (FSH) may be tested1.

Premature Ovarian Insufficiency Most women have a fixed number of eggs and when these run out the menopause starts. But some women have less than the normal number of eggs to start with and these women suffer premature ovarian insufficiency. Effectively, they have an early menopause.

Bio-Identical versus Body-Identical Hormone Replacement Therapy These are complex and confusing terms3,4,5 Celebrity endorsement by beautiful people is the sort of trap that any woman keen to preserve her youth and beauty can fall into. The arguments seem persuasive in that a product is said to be ‘natural, ‘not a drug’, ‘harmless’ and that, added to ‘look how fabulous I (the Celebrity) am and remain despite my age’ is very powerful. This is one of the key issues with bio-identity and biosimilarity with hormones. There are hormones we naturally produce, there are hormones that animals produce that are close to ours and

there are synthetic hormones that are close to our own. A lot of bad press has come from the animal hormones. Premarin was used in the Women’s Health Institute (WHI) study6. The equine oestrogens are different enough to give us problems but surely synthetic versions of our own hormones could not be bad? Well it depends on how similar they really are and we now know that some bio-identicals affect receptors other than pure oestrogen ones and as a consequence cause acne, bloating etc. The basis of the trend for private bio-identicals/ body identical hormones requires testing, which

“Bio-identical hormones” are precise duplicates of estradiol, estriol, estrone,

The specialist online research resource for General Practitioners and other senior primary care professionals

progesterone, DHEA and testosterone as synthesised by the human ovary and adrenal. However, this is a marketing term and bios is a Greek term referring to “life”. A more accurate way to refer to these hormones is “body identical.”2

Visit: www.primarycarereports.co.uk

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

The National Institute for Health and Care Excellence (NICE) are clear that no testing is required for the menopause and that the diagnosis is based on symptoms only

Hormone therapy may consist of either unopposed estrogen or a combination of estrogen and progestogen. Unopposed estrogens include conjugated equine estrogen (CEE), ethinyl estradiol (EE), micronized 17B-estradiol (E2), estradiol valerate (EV), estrone sulphate (EIS) and esterified estrogens (ESE). These estrogens cannot be considered equal. They vary in their dose equivalency and have different metabolic effects on different tissues or end organs. In order to make meaningful comparisons, estrogens need to be grouped into low moderate and high doses according to the advice of experts (France 1998; MacLennan 1998; Ansbacher 1994; O’Connell 1998). There are a number of different progestogens used in hormone therapy, which can be classified according to their structure and/or bioactivity (Maitra 2004). These include • micronized progesterone (MP), dydrogesterone (a retroprogesterone), and progesterone derivatives such as medrogestone (MG). • pregnanes such as medroxyprogesterone acetate (MPA), megestrol acetate (MA), cyproterone acetate (CPA). • norpregnanes such as trimegestone (TMG), nestorone and promegestone. • estranges such as norethisterone, norethisterone acetate (NETA) and lynestrol, derived from testosterone and collectively known as first generation progestogens. • gonane progestogens which can be divided into 2 categories – the secondgeneration progestogens such as norgestrel, levonorgestrel (LNG) and the third generation progestogens such as desogestrel (DG), gestodene, norgestimate (NGM) and dienogest. • drospirinone – a new progestogen derived from spironolactone not included in the generation classification. Some progestogens are prodrugs which are metabolised by the liver into active compounds. Examples are promegestone.,which is converted to trimegestone, and norgestimate which is convertedto norgestrel.

NICE specifically advises us to avoid. The tests of saliva are supposed to measure x or y or z and replace it with something very similar to what we would naturally have produced.

The Wise Woman’s Dilemma Imagine walking down a street trying to decide on HRT. There are 2 shops to choose from. One has the NICE logo and says ‘Tell us your symptoms, no need for tests and you will get NHS prescribed HRT based on your needs. We would like to check on you after 3 months to see how you are getting on.’ The other, more glamorous shop says ‘Reassuringly Expensive. Pop in for complex tests and we will make up a hormone cocktail based on your personalised deficiencies.’ Fanciful? No, since this is the choice posed to every woman who reaches menopause. Your role as the General Practitioner is to make sense of this and to give some quality control advice. Scare stories in health are fodder for certain newspapers. One newspaper revels in two key health stories: 1) something 10 | WWW.PRIMARYCAREREPORTS.CO.UK

very ordinary is much more deadly than you know and 2) scientists have found a miracle cure for something very debilitating. Of course, neither story is typically true because life and science are more complicated than that. The symptoms of menopause are common, debilitating and there is a relatively inexpensive and safe cure. Two infamous and influential studies (one for the WHI) caused much concern in the HRT world and provided (and still do) much fodder for the less scrupulous press. First, we need to remember to compare like with like. Panay notes that the WHI study used ‘an overdosage of hormones in a relatively elderly population1‘. The other issue is that the women were using horse-derived hormones, something that we no longer do. So these studies used a higher dose of the wrong hormones in an older age group. The problems identified were increased risk of cardiac disease and stroke. But when modern, lower dose, non-horse hormones are used in younger age groups these problems do not occur.


MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

Types of HRT – Different Oestrogens and Progestogens We can already see that HRT is not a homogeneous group. We no longer use horsederived hormones so where else do we get it from? Well, we can get it from plants or we can synthesise it. Both are ‘natural’ since the synthesised product can be made the same as what we would have produced ourselves (body-identical). The complexity comes from those private practitioners or private pharmacies that ‘make up’ a personalised cocktail and call it bio-identical.

A Womb of One’s Own We now know to ask or discover if a woman has a womb, since oestrogen alone in such a case would lead to endometrial thickening with an increased risk of cancer. A womb needs progesterone or progeston to reverse the negative effects of excess oestrogen. If women do not have a womb then oestrogens alone will suffice.

Primary Care Reports

Summary A woman with an intact womb in menopause needs a cocktail of oestragens and progesterone/ progestagen. Like our favourite 007 fictional spy, her cocktail should leave her symptoms shaken but not stirred and she needs no expensive olive on top.

References:

h  ttps://www.nice.org.uk/guidance/ng23/chapter/Recommendations#diagnosis-of-perimenopause-and-menopause

http://www.pms.org.uk/professionals/hormones Accessed 17/7/2017

https://menopausedoctor.co.uk/early-menopause/body-identical-hormones/ Accessed 17/7/2017

http://www.health.harvard.edu/womens-health/bioidentical-hormones-help-or-hype Accessed 17/7/2017

http://www.mariongluckclinic.com/our-services/bio-identical-hrt Accessed 17/7/2017

http://jamanetwork.com/journals/jama/fullarticle/195120 Accessed 19/7/2017

1

Accessed 19/7/2017 2 3

4 5 6

Furness S, Roberts H, Marjoribanks J, Lethaby A, Hickey M, Farquhar C. Hormone therapy in postmenopausal

7

women and risk of endometrial hyperplasia. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.:

CD000402. DOI: 10.1002/14651858.CD000402.pub3.

A woman with an intact womb in menopause needs a cocktail of oestragens and progesterone/progestagen

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

Vasomotor Symptoms, the Diagnostic Pathway, Life Style Changes, Mental Health, Sexual Pleasure and the Menopause Dr Charles Easmon, Editor

When a woman over 45 walks into your surgery, the menopause should be top of your list of working diagnoses

A

MAN with a sweaty red face is not an attractive proposition. Imagine what it is like for women as they age to go from normality to this fate when their egg production stops. To feel hot and uncomfortable in work and social situations is unpleasant and affects confidence. It is likely to lead to avoidance and isolation. The mechanism behind the vasomotor effects of menopause seems to be a product of vasodilation and a change in thermoregulation caused by the hormonal changes and these can be relatively easily reversed by low doses of oestrogen and progesterone. The National Institute for Health and Care Excellence (NICE) make it clear that if and when women present with these menopausal symptoms they should be offered Hormone Replacement Therapy (HRT) without the need for blood tests. HRT is also known as Menopausal Hormonal Therapy (MHT) and in 2013 a useful Global Consensus on MHT was published, which was revised in 20161. When a woman over 45 walks into your surgery, the menopause should be top of your list of working diagnoses and, based on NICE guidance, if she has vasomotor symptoms and irregular periods, you can advise her on HRT since she is in the perimenopause. If she is not on hormonal contraception and has not had any periods for at least 12 months then she is in the menopause. If for any reason she has no uterus (surgical or congenital etc) then, again, you know that she is in the menopause. If there is a family history of early menopause (before aged 45) then take this into account, as

this may be a case of premature menopause. NICE recommends blood tests in only 2 situations and for everyone else there is no point in wasting expensive NHS resources. The two situations are to do a Follicle Stimulating Hormone (FSH) level:

The Ideal GP Menopause Consultation (Based on NICE Guidelines) First you would explain the stage, common symptoms and life-style changes that can affect or improve the menopause experience. Then you would explain the benefits and risks of treatment with HRT and the long-term effects on untreated menopause. The symptoms can be looked at as vasomotor, musculoskeletal, water works effects, mood effects and sexual. In the vasomotor part are the sweats and hot flushes. In the musculoskeletal part there are joint and muscle pains. In the waterworks part there are problems with vaginal dryness. In the mood part is low mood, which is easily mistreated with anti-depressants. In the sexual part is low desire. For treatment, HRT or CBT or the two together may be useful for women. A non-hormonal drug option is the use of the drug clonidine. Various useful websites can help the women better understand menopause and these include: • https://thebms.org.uk/ • http://www.pcwhf.co.uk/publications.html • http://www.menopausedoctor.co.uk/ • http://www.menopause-exchange.co.uk/

‘in women aged 40 to 45 years with menopausal symptoms, including a change in their menstrual cycle in women aged under 40 years in whom menopause is suspected2’

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MANAGING MENOPAUSAL SYMPTOMS AND THE ROLE OF HORMONE REPLACEMENT THERAPY

Primary Care Reports Contraception should be discussed with both perimenopausal and menopausal women. Ideally, pre-cancer and pre-uterine surgery patients should be counselled on both the menopause and future fertility. The vasomotor symptoms respond well to combined oestrogen and progesterone in women with a uterus but for those without a uterus the recommendation is to have only the oestrogen component. If lack of sexual desire is the issue, then testosterone can help. For urogenital dryness/atrophy then topical oestrogen with or without oral HRT is recommended and this may be alongside vaginal lubricants and ointments.

Things to Avoid in the Menopause Most importantly, the routine use of antidepressants should be avoided. NICE advises against the use of selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or clonidine as first-line treatment for vasomotor symptoms alone. Blood tests are unnecessary except in exceptional circumstances as above. Your obese patients (BMI over 30) and those with other risks of venous thromboembolism are best advised to be on transdermal rather than oral HRT since the risk of this is no greater than the risk of those on no HRT.

Complimentary Medicines You are almost bound to be asked or informed about complimentary medicines but there is limited data on their efficacy, purity, constituents and side effects.

Mental Health, Sexual Pleasure and the Menopause A snappy, irritable person soon loses friends and alienates people but what if the problem is not the person but their hormones? A low mood, poor sleep, and negative thoughts are classic symptoms of depression and it is very tempting to encourage all such people to take what may be life-long anti-depressant drugs. These drugs are not a cure and simply modify symptoms. But what if the prescribed treatment of antidepressant drugs was wrong and women in these circumstances should instead be prescribed HRT as per NICE guidance? General Practitioners must listen long, hard and more carefully to their women patients because the practices of yesterday should not be the practices of today when we have so many supportive evidence-based treatments and advice available. Pain during intercourse, partly caused by vaginal dryness, can be alleviated by topical oestrogen therapy.

Summary Menopausal women suffer but, in HRT, we have a safe and practical solution that can be adhered. We can rely on the woman’s history and, generally, we do not need to do blood tests. The HRT can be oral or topical or both as required. As a GP, it is important to listen and reflect. Women will have many concerns and many questions and these issues should not be dismissed but weighed and considered based on available evidence. Finally, remember that you are not alone and, for those cases where you are unsure, there will be local specialists to refer to in this area.

References: T. J. de Villiers, J. E. Hall, J. V. Pinkerton, S. Cerdas PĂŠrez, M. Rees, C. Yang & D. D. Pierroz (2016): Revised Global Consensus Statement on Menopausal Hormone Therapy, Climacteric, DOI: 10.1080/13697137.2016.1196047

1

 https://www.nice.org.uk/guidance/ng23/chapter/Recommendations#diagnosis-of-perimenopause-and-menopause Accessed 19/7/2017

2

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Primary Care Reports – Managing Menopausal Symptoms and the Role of Hormone Replacement Therapy  

Primary Care Reports – Managing Menopausal Symptoms and the Role of Hormone Replacement Therapy – Besins Healthcare (UK) Ltd

Primary Care Reports – Managing Menopausal Symptoms and the Role of Hormone Replacement Therapy  

Primary Care Reports – Managing Menopausal Symptoms and the Role of Hormone Replacement Therapy – Besins Healthcare (UK) Ltd