Abstract
Women choose to see a clinician with menopause expertise for all sorts of reasons and sheer desperation will feature among them. There are unfortunately few options if their GP is just not listening or is at the limit of what they feel confident to manage. In very rural southwest England, there are no multidisciplinary menopause specialist teams. For my population, the NHS has chosen not to support expertise at all. I worry for the future as knowledge and 30 years’ experience are difficult to gain. Sometimes you just need to draw on this experience to work pragmatically and from first principles. Women are not all the same. We are advised to personalise management and some may require a very individual solution. This does not have to be clever or complicated or costly but by getting it right can give the patient her life back. The benefit to the health economy is the saving of repeated attendance and multiple inappropriate prescriptions or procedures. An example: Hilary is 62.
Her first period was at the age of 13 and from the outset they were irregular and bleeding lasted for seven days. Periods stopped altogether for 12 months at the age of 21 while travelling. At the age of 26, she had a planned pregnancy. Afterwards, periods were irregular and infrequent with intrusive severe premenstrual symptoms and prolonged bleeding. She failed to conceive a second time despite clomiphene and then IUI and decided not to proceed to IVF.
Her PMS progressively became worse and night sweats and sleep disturbance appeared in addition to the mood symptoms. Someone prescribed Danazol. This is a synthetic testosterone derivative which blocks ovulation and suppresses endometrium. It is rarely used today as for many women its use is limited by androgenic side effects. For her, it was liberating. It stopped her PMS, bleeding was minimal and she was promoted at work.
Hilary took this to age 54 and was then persuaded to stop. She had noticed an increase in night sweats and change in body shape and agreed that she was menopausal. However, on stopping, the flushes became very frequent (every 20 min) and severe. She lost confidence and became indecisive, tearful and irrational. She decided that she had to stop work as she held a position of responsibility and just could not function. There was a little bleeding but this stopped very soon.
Hilary was prescribed cyclical conjugated estrogens and norgestrel a year later but although the estrogen helped, the progestogen component was not tolerated as it badly affected mood. She was changed to continuous conjugated estrogens with medroxyprogesterone acetate but then bled persistently and stopped taking it. She continued to be overwhelmed by flushing and tried clonidine without relief.
Hilary was advised in 2014 to have removal of her ovaries – as a risk reduction strategy as her mother had had ovarian cancer. The prospect alarmed her and she agreed though an ultrasound had been normal. She was warned that flushing might increase but this did not happen: her flushes simply continued to be awful.
Having moved to the southwest in 2015 Hilary’s new GP suggested venlafaxine at very low dose (37.5 mg/day). This does have evidence of some benefit for flushing but is not licensed and not recommended by NICE as first line. When increased to twice a day, this took the edge off but did not solve the problem. When the flushing seemed to be returning to its original level, she came to me to discuss her options. She had flushed solidly for eight years and hoped that there might possibly be something that could help as it continued to impact on her life.
The only medication Hilary took was Venlafaxine 37.5 twice daily. There were no other features of her personal or family history that were relevant.
Despite the SNRI, Hilary was having up to four sweats at night with no evident pattern and daytime flushes in the morning and evening. Sleep was disturbed in addition to the night sweats and she was out to the toilet up to three times. Mood was reported to be more stable than it had been five years before when irritability and confidence had been a significant problem. Libido was not stated to be an issue.
We will never now be able to prove it, but I wondered whether Hilary originally had a polycystic ovarian syndrome but was very intolerant of progesterone when she did ovulate. She had been intolerant of both norgestrel and medroxyprogesterone acetate in HRT.
Low levels of estrogen clearly had affected her after delivery and before periods. The pattern gave some clue as to why menopause proved to be such a problem. Replacing estrogen had helped in the cyclical preparation it was the progestogen that was not tolerated.
Removing postmenopausal ovaries would have in addition depleted endogenous testosterone. This could be a problem in itself, but also through reduced conversion to estrogen. It was very reasonable to warn that this might have made the situation worse.
Previously, androgens had seemed to have a positive effect whether as endogenous testosterone or the effect of the Danazol. This in isolation is somewhat unusual. Danazol has little progestogenic effect and must have simply blocked ovulation and thereby suppressed endometrium. It worked for her.
Because of this my suggestion was Tibolone 2.5 mg daily. I regard this as a synthetic steroid prodrug which is converted within target cells to a derivative that works like estrogen, testosterone or progesterone depending on the cell. Both published research and experience suggested that it was least likely to be associated with bleeding. I suggested to her that if it was going to help benefit should start within two weeks but could take six to eight weeks to have its full effect.
There was no evident reason not to take this approach. Hilary had a BMI of 24.6, a normal blood pressure, did not smoke and drank only the very occasional gin and tonic as this exacerbated the sweating less than wine. We talked about the possible small risk of breast cancer.
Hilary had put up with the sweats for years and had given up a significant part of her life because of them. She had been very well when taking the Danazol and wanted to try Tibolone. We agreed a review at three months.
When seen again, Hilary was very happy. She reported that her persistent and pervasive flushing had started to improve within two weeks and was settled by three. At worst, she had the odd warm spell, she was staying asleep, mood was buoyant and sex had become not just possible but a pleasure again. There had been no bleeding or bladder problems and both energy and stamina had improved. Reassuringly, she had had both bowel and breast screening which were negative. We discussed a very slow withdrawal from the venlafaxine.
The plan is to continue with annual review but to anticipate that dose reduction might become possible with time. The aim is the lowest effective dose but there is no arbitrary limit to treatment. Provided that the perceived benefit outweighs the perceived risk, Hilary can make an informed decision to continue.
The GP can carry this on but by her own admission did not know what to do and we can now work together. There is most definitely a place for an expert.