Prescribing hormone replacement therapy: key considerations for primary care physicians

The last few years has seen a dramatic rise in the number of women seeking advice for the menopause and hormone replacement therapy (HRT).¹ Navigating the complexities of HRT and being able to discuss the options available in primary care is, therefore, essential. The aim of this article is to provide key considerations for primary care physicians (PCPs) when considering HRT implementation and also the role of testosterone and vaginal oestrogen for symptom management (Figure 1). It is beyond the scope of this article to discuss the role of tibolone, selective oestrogen receptor modulators (SERMs), and dehydroepiandrosterone (DHEA) for managing menopausal symptoms, and PCPs would be encouraged to seek specialist input prior to commencing these treatments.

Figure 1.

Flowchart of key considerations when commencing HRT.

BD = two times a day. HRT = hormone replacement therapy. OD = once a day. TDS = three times a day.

KEY CONSIDERATION 1: IS HRT APPROPRIATE?

Although hot flushes and night sweats are commonly associated with menopause, a wide plethora of symptoms including brain fog, insomnia, and reduced libido have been reported.² Although HRT has been shown to be beneficial for symptomatic women who are peri-menopausal (last menstrual period [LMP] within last 12 months) or menopausal (more than 12 months since last LMP), a holistic review of lifestyle factors and exploring natural or herbal therapies is crucial prior to its implementation. Contraindications to its use include previous or current history of hormone-sensitive breast cancer, endometrial cancer, and endometrioid ovarian cancers.³ Potential alternatives in these cases include gabapentin, pregabalin, clonidine, and venlafaxine, and can be started in primary care following a risk versus benefit discussion.

KEY CONSIDERATION 2: WHAT PREPARATION AND REGIMEN ARE REQUIRED?

Once the decision is made to commence HRT, it is important to consider whether a combined oestrogen/progesterone or oestrogen-only preparation is required. For all women with an intact uterus, the former is vital for reducing the risk of endometrial hyperplasia.

While combined HRT is available as either a sequential or continuous regimen, the preparations vary by the type of progesterone used and dose of oestrogen. With the management of menopausal symptoms determined by the latter, prescription is often guided by availability. While both sequential and continuous combined regimens deliver a daily dose of oestrogen, sequential regimens deliver progesterone for up to 12 days per month (compared with continuous regimens that deliver a daily dose). Sequential regimens are recommended for peri-menopause to reduce the risk of breakthrough bleeding and these women should be counselled that they may experience a withdrawal bleed on their progesterone-free days. Generally, women can be switched from a sequential to a continuous regimen after 2 years if they are below the age of 50 years, or after 1 year after the age of 50 years.

KEY CONSIDERATION 3: WHAT IS THE MOST APPROPRIATE ROUTE AND DOSE OF HRT TO START ON?

Once the preparation and regimen have been decided, the next step is to choose the route and dose of HRT. With HRT available either as an oral or transdermal preparation, the latter bypasses first-pass metabolism of the liver and is suitable for women with a history of venous thromboembolism (VTE), liver disease, malabsorptive diseases, and migraines.⁴ Available as a patch, gels (EstroGel, Sandrena), or spray (Lenzetto), transdermal preparations are also favoured for women with a BMI>30. For those with a BMI>40, referral to a specialist menopause clinic would be recommended.

The patch is available as either oestrogen only or as a combined oestrogen/progesterone patch, is applied to the thighs, and changed on a twice weekly basis. In contrast, EstroGel, Sandrena, and Lenzetto are oestrogen only and are applied every day. With the exception of Lenzetto, which is applied on the arms, EstroGel and Sandrena are applied to the thighs. Additional progesterone cover must therefore be prescribed separately for those with an intact uterus, and further information on dosage and options for progesterone cover are provided in Table 1.

Table 1.

Progesterone cover for HRT

Progesterone	Comments	Side effects	Sequential combined regimen	Continuous combined regimen
Oral
Utrogestan	Micronised progesterone, bio-identical and helps with sleep and safe for those with previous history of VTE and migraines	Nausea Fluid retention	200 mg for 12 days per month, to take at night	100 mg every night
Desogestrel	Contraceptive action Off-licence use and not first line	Nausea Fluid retention	150 mg daily	150 mg daily
Medroxyprogesterone	Use with caution with previous history of hormone-sensitive breast cancer, VTE, and migraines	Mood changes Fluid retention Breast tenderness	10 mg daily for 12 days per month	Minimum of 2.5 mg daily up to 5 mg daily
Norethisterone	Use with caution with previous history of hormone-sensitive breast cancer, VTE, and migraines	Mood changes Fluid retention Breast tenderness	5 mg for 12 days per month	5 mg daily or consider Noriday 3 tablets daily.
Intrauterine contraceptive device
Mirena	Can remain in situ for 5 years (off-licence use) for endometrial protection and contraceptive cover	Irregular or heavy bleeding more commonly seen within first 4 months of insertion.	NA	NA

HRT = hormone replacement therapy. VTE = venous thromboembolism.

The starting dose of oestrogen should be guided by age, with women below the age of 50 years generally requiring high doses compared with women between 50–59 years, who may note alleviation of their symptoms at low or medium doses. It is also advised that HRT should be commenced for women over the age of 60 years or more than 10 years from their LMP at low or ultra-low doses and transdermally.⁵ To reduce the risk of oestrogenic side effects (bloating, breakthrough bleeding, nausea, and headache), it is recommended that all women should start on a lower dose initially and be reviewed at 4 months and thereafter, at a minimum, annually to ensure symptom management. While it is beyond the scope of this article to provide a detailed breakdown of all the different types and doses of HRT available, a prescribing guide outlining the oestrogen dose equivalence between some of the products available is provided in Table 2.⁶

Table 2.

Guide for prescribing HRT

HRT	Regimen	Oestrogen strength
		Ultra-low	Low	Medium	High
Oral (once a day tablets)	Oestrogen only	Alternate-days Elleste Solo 1 mg or Zumenon 1 mg	Elleste Solo 1 mg Zumenon 1 mg	Elleste Solo 2 mg Zumenon 2 mg	Elleste Solo 2 mg & 1 mg Zumenon 2 mg & 1 mg
	Sequential combined		Elleste Duet 1 mg Femoston 1/10	Elleste Duet 2 mg Femoston 2/10	Elleste Duet 2 mg & Elleste Solo 1 mg
	Continuous combined	Femoston Conti Low	Femoston Conti Kliovance	Elleste Duet Conti 2 mg Kliofem 2 mg	Elleste Duet Conti 2 mg & Elleste Solo 1 mg
Patch (applied on thigh and changed twice weekly)	Oestrogen only	½ Evorel 25 patch ½ Estradot 25 patch	Evorel 25 Estradot 25	Evorel 50 Estradot 50	Evorel 75/100 Estradot 75/100
	Sequential combined	½ Evorel 25/Estradot 25 patch & Utrogestan 200 mg for 12 days/month	Evorel 25/Estradot 25 & Utrogestan 200 mg for 12 days/month	Evorel Sequi Femseven Sequi	Evorel Sequi & Evorel or Estradot 25/50
	Continuous combined	½ Evorel 25 or Estradot 25 patch & Utrogestan 100 mg every night	½ Evorel Conti patch ½ FemSeven Conti patch	Evorel Conti FemSeven Conti	Evorel Conti & Evorel or Estradot 25/50
Estrogel (daily application to thigh)	Oestrogen only	½ pump	1 pump	2 pumps	3‒4 pumps
Sandrena (daily application to thigh)	Oestrogen only	½ 0.5 mg sachet	0.5 mg	1 mg	1.5‒2 mg
Lenzetto (daily spray to arms)	Oestrogen only	1 spray	2 sprays	3 sprays

HRT = hormone replacement therapy. Blacked out cells = no option.

KEY CONSIDERATION 4: IS TESTOSTERONE OR VAGINAL OESTROGEN REQUIRED?

Testosterone

Testosterone supplementation on its own is not recommended because of the side effects of bloating, acne, and hair growth.⁷ While switching women from oral to transdermal HRT can increase the levels of free circulating testosterone, testosterone supplementation is recommended for women who continue to experience low libido and fatigue despite adequate oestrogen replacement.⁷ Contraindications to its use include active liver disease and hormone-sensitive breast cancer. Prior to its implementation, discussion with a specialist menopausal service would be recommended and total testosterone levels should always be checked prior to commencement and again 6‒12 months after initialising therapy with the aim of keeping levels within the female’s physiological range. With testosterone implants becoming increasingly difficult to source, transdermal preparations available in the UK can either be administered daily or on alternate days. Application should be on the thighs but not over the same area if transdermal HRT is concurrently being used.

Vaginal oestrogen

With vaginal oestrogen now available over the counter, its use is recommended for women experiencing genitourinary symptoms such as vaginal dryness, superficial dyspareunia, vulvovaginal irritation, and increased urinary frequency and urgency. Available either as a pessary or a cream, women should be advised to commence on a daily dose for 2 weeks before being gradually reduced every 2 weeks and can remain on a lifelong twice-weekly or once-weekly regimen. For women with a previous or current history of breast cancer, input from a specialist menopause service would be recommended prior to commencing vaginal oestrogen.

It is recognised that prescribing HRT can be challenging within primary care. By providing a breakdown of the key considerations, the aim is that this can guide PCPs to be more confident in initialising HRT and seeking specialist input when appropriate.

Funding

There was no additional internal or external funding for this project.

Provenance

Freely submitted; externally peer reviewed.

Competing interests

Rima Chakrabarti is a member of the British Menopause Society (BMS).

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