Levels of female reproductive hormone will start to become less predictable and then drop; sometimes gradually with age, sometimes abruptly as a result of disease or medical treatments.
The transition typically kicks off naturally from about the mid- 40’s and the symptoms resulting from hormone derangement or loss are commonly referred to as “The Menopause” by patients and HC (even though we know that the word ‘menopause’ actually means “end of the monthly”). So while menopause officially is defined as the last ever natural menses and most commonly occurs in the early 50’s, the symptomatic phase of the lead into sex hormone changes – more accurately referred to as ‘perimenopause’, often precede the final menstrual period by many months or even years. We use those terms interchangeably. This transitional time (‘Perimenopause’) puts some patients in the unenviable position of having to juggle midlife hormonal symptoms as well as contraceptive concernsfertility may decline in your 40’s & 50’s but it’s not gone!
Some but thankfully not all patients struggle with perimenopausal symptoms and seek our advice in primary care. The amount of issues that may be uncovered in a first menopause visit are legion.
The classic physical symptoms are easily recognized: night sweats, hot flushes, heavy and/ or irregular periods, loss of vaginal elasticity and lubrication, decrease in metabolism (+/- weight gain), hair and skin changes, joint complaints, bladder complaints, et al.
The psychological symptoms are just as prevalent and possibly more likely to be misinterpreted. They include; depression, mood swings, anxiety, irritability/ rage, tiredness, memory loss, poor concentration, loss of libido, PMStype symptoms, et al.
The first thing to do is confirm the diagnosis. Easier said than done as hormone blood tests are often within normal ranges for perimenopausal patients and so are not recommended as having any part in the diagnostic process. In addition, not everything a patient experience in their middle life is related to perimenopause hormones changes. It can be challenging to identify whose mood symptoms are arising directly from the perimenopause vs. pre-existing mood issues being exacerbated by the approach of menopause. A thorough history – maybe even expedited by pre consult symptom self-assessment questionnaires- may be of use. The most effective treatment for menopause related symptoms is HRT but it is not a ‘miracle cure’ and some people won’t need it, won’t want it or have been advised to avoid it. Clinicians are reminded that menopause care should be individualised- using a comprehensive approach that pays attention to advice on exercise, optimising weight, stopping smoking, and reducing alcohol consumption as well as management options such as HRT.
Talking about Thrombosis
One of the more important aspects of the history taking (apart from a kind ear which is of immeasurable benefit) is the need to exclude comorbidities that might affect the range of treatment options available to that patient. Some people will be keen to consider menopause hormone balancing or replacement therapy for their menopause symptoms (MHT or HRT). MHT involves providing small dose of estrogen in all cases and usually some low dose progestagen for the patient with a uterus. Occasionally, in cases of hypoactive sexual desire or arousal, some testosterone may also be offered. Each of these
individual hormones come with their own lists of contraindications and special precautions. Some contraindications are absolute but some special situations mainly require a conversation with either a menopause specialist or the consultant team that manages the patient’s medical condition; this is according to the British Menopause Society. One such situation is in the case of patients with a personal past history of thrombosis. If a perimenopausal patient who has had a VTE has considered and/ or explored nonhormonal options for managing their symptoms and now is keen to consider HRT, they can but we need to be much more cautious when prescribing for them. Our first job is to make sure as much is being done to optimise any modifiable risks that they carry. We know venous thrombosis particularly can be liked to modifiable issues such as:
– Immobilization
– Smoking- Long plane or car trips of more than 4 hours &
– Certain contraceptives – any high-dose, strong estrogen – like the ones in all the combined pills, rings and patches – can increase thrombosis risk; similar to the elevated risk linked to being pregnant. Some progestagens have been linked to increased VTE risk too, but not at the typical doses we see in progestagenonly contraceptives.
So keeping active and reducing or stopping smoking, keeping hydrated and avoiding the avoidable triggers is an important part of a menopausal chat for someone with a past history of VTE.
Now traditionally the estrogen in HRT was considered contraindicated for people with a past history of VTE as we expected the estrogen in HRT to have a similar effect on clotting mechanisms to the estrogens in contraceptives. High levels of estrogen (and certain progestagens) in the blood can be ‘Pro- thrombotic’. Oral oestrogen goes straight from the GI tract to the liver, where it is metabolized. During this first run through the liver is where the impact on clotting molecules occurs. But even non oral estrogens can impact clotting risk if the doses are high or the estrogen molecule is particularly potent – so the contraceptive patch and vaginal ring are just as likely to promote VTE as oral contraceptive pills. Risk is maximally elevated at initiation – when a patient is commencing an estrogen containing contraceptive – and wanes with time, so using estrogen based contraceptives for a short time is not safer than staying on them for months or years. In addition, every time a patient switches brands or comes off for a few weeks or months ‘to see if everything is still working in there’, they increase their clot risk when they restart.
So, knowing all this it was only logical that we assume HRT – type estrogen would also be risky for women with elevated VTE risk?
Well, apparently this is not the case.
While it is true that the estrogens in ORAL HRT can increase clot risk, there is an abundance of research to confirm that lowdose, ovarian – similar HRT oestrogen does not affect clot risk when used transdermally. This is supported by all the menopause guideline groups as well as by the gynaecology and haematology guidance groups. The go-to data to support this is the nested case-control study by Yana Vinogradova, et al that looked at women diagnosed with VTE between 1998 and 2017. Ref 2 With regard to progestagens, this study did not actually review micronized progesterone for some reason, but it did look at dydrogesterone and found it also to be a safer option when there is concern about blood clots.
So we tell patients this:
while people who are smoking, overweight or who have had a blood clot in the past should not use estrogen contraceptives nor should they use oral estrogen in HRT, they can safely try transdermal estrogen HRT products, in modest doses after discussion with their haematologist or menopause specialist.
According to the UK’s National Institute for Health and Care Excellence: ‘The risk of venous thromboembolism (VTE) is increased by use of an oral oestrogen-containing HRT product compared with baseline population risk, but the risk associated with transdermal HRT given at standard therapeutic doses is no greater than baseline population risk.’
Be warned though; the information leaflets that come with transdermal HRT estrogen products (and even with local vaginal oestrogen, which has never been suspected of increasing DVT risk) say: May cause blood clots or Do not use if you are at risk of blood clots. So patient counselling is key.
If someone is already on an anticoagulant, they may also consider low dose transdermal HRT oestrogen.
1. National Institute for Health and Care Excellence. Menopause: diagnosis and Management. NICE, 2015
2. Vinogradova Y, et al. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019 Jan 9;364:k4810. doi: 10.1136/ bmj.k4810. Erratum in: BMJ. 2019 Jan 15;364:l162. PMID: 30626577; PMCID: PMC6326068.
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