Is the menopause transition managed as well as it could be in women with chronic kidney disease including those undergoing renal transplant? One of the most under-recognised and neglected patient problems in clinical nephrology

The case

Carol, age 50 had a telephone consultation following referral to my specialist menopause clinic, at her request. She became amenorrhoeic at age 37, following her second renal transplant. Despite menopausal symptoms (hot flushes and night sweats), no-one ever talked to her about menopause management and as she felt so much better in herself following her successful transplant, she was prepared to put up with the sweats, which were balanced by the benefits of no longer bleeding. Seventy per cent of menopausal women are still having hot flushes after seven years. Interestingly, symptoms which can be associated with a feeling of doom are rated similar to CKD.

Thirteen years later, Carol requested referral to a specialist menopause service after a menopause update in her workplace, where the longer-term consequences of estrogen deficiency in otherwise healthy women (reduction in bone mineral density and increase in cardiovascular risk) were highlighted.

A successful transplant with restoration of the hypothalamo-pituitary-ovarian axis should reinstate normal ovarian function with a need for contraception if required. However, there has been no research undertaken to establish the average age of menopause in women experiencing a successful renal transplant. Gonadotrophin levels were not checked in Carol’s case and one must assume that she was menopausal at the age of 37, in the absence of any objective means of establishing a diagnosis.

Presenting complaint

Concern regarding cardiovascular health

Minimal problems with vasomotor symptoms

Smear tests painful

Recent UTI with sepsis requiring admission to hospital

Past medical history

Hypertension – now controlled with medication. Blood  pressure reading at referral November 2019 – 120/70

Glomerulosclerosis

CKD (Stage 5)

Peritoneal dialysis 1995–1996, complicated by  encapsulating sclerosis of the peritoneum

Cadaveric renal transplant 1996 – failed 2000

Haemodialysis 2000–2007

Cadaveric renal transplant 2007

Secondary hypoadrenalism

Osteoporosis then osteopenia

Social history

Ex-smoker – stopped when developed renal failure

Excess alcohol consumption before developing  renal failure

Was overweight (BMI now 20)

Works in the catering department of a large  department store (currently shielding due to  Covid 19 pandemic)

No partner

Drug history

Cholecalciferol 20,000 U every three weeks

Calcichew D3 forte

Sodium bicarbonate 500 mg bd

Doxazosin 4 mg 1 twice daily

Irbesartan 150 mg daily

Tacrolimus 2.5 mg bd*

Azathioprine 25 mg daily

Prednisolone 4 mg daily

Bisphosphonate infusion three times a year

*In women taking both tacrolimus and menopausal hormone therapy (MHT), tacrolimus toxicity has been noted and LFTs and calcineurin inhibitor concentrations should be closely monitored. ¹

Premature ovarian insufficiency caused by CKD is under-recognised with no reference to CKD as a potential cause in two review papers on premature ovarian insufficiency.^2,3 A review paper focusing on menopause in CKD by Vellanki and Hou ¹ highlights that the long-term effects of menopause are ‘one of the most under-recognised and neglected patient problems in clinical nephrology’. CKD is associated with disruption of the hypothalamo-pituitary-gonadal axis, possibly due to the influence of uraemia on atresia of ovarian follicles, resulting in a reduction in circulating estrogen levels and early onset menopause (Figure 1).

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Figure 1.

Pathophysiology of menopause in women with and without CKD. CKD: chronic kidney disease; FSH: follicle stimulating hormone; LH: luteinising hormone. Source: Taken from AJKD, in Practice. ¹

For Carol, 13 years post menopause, I felt (following discussion with my remote renal physician) that any potential benefits associated with systemic MHT were outweighed by the three-fold increase in risk of cardiovascular disease (CVD) associated with CKD. She reported minimal systemic symptoms of menopause and her main concerns related to her increased risk of osteoporosis and CVD. She has responded well to bisphosphonate infusions, moving from osteoporosis to osteopenia. Her cardiovascular risk would be better addressed by the addition of a low dose statin in preference to MHT more than 10 years post menopause. Statins can also have a beneficial effect on bone mineral density. I also felt that locally delivered vaginal estrogens could reduce the risk of further UTI and improve comfort for future cervical smear tests and possible sexual activity if she should meet a new partner.

Although otherwise healthy women benefit from treatment with MHT, there are no data for women with CKD or in women who have had a renal transplant. This limits treatment options for those women, with a knock-on negative effect on quality of life if they remain untreated.

Recommendation: Women with CKD stage 3–5 should have a serum FSH level checked if they are amenorrhoeic and this should be repeated after 4–6 weeks if elevated.

MHT in CKD

CKD is known to alter the pharmacokinetics of exogenous estrogen with an increase in systemic levels and therefore a 50% lower dose is recommended and as with any other concomitant medical problem, this is best delivered transdermally to reduce the risk of venous thromboembolism. MHT has not been reported to result in deterioration of allograft function in renal transplant patients.

Epilogue

This case highlights the potential for managing the menopause without the need for face to face consultations, even in more complicated cases. In addition, it highlights the need for a multidisciplinary approach in women with CKD, which can be facilitated using virtual platforms such as Microsoft Teams. Before the Covid 19 pandemic, it is unlikely that these alternatives to traditional face to face consultations and face to face MDTs would have been considered in day to day UK clinical practice.