Starting HRT is the beginning of a clinical process, not a one-time event. The first prescription is deliberately cautious: starting doses are conservative to minimise initial side effects, formulations are chosen from a standard set rather than tailored from the outset, and the body's response is not predictable enough to get things optimal immediately. Most women require at least one dose or formulation adjustment within the first year, and some require several before reaching a regimen that works well.

Knowing what good ongoing care looks like (what should be reviewed and when, and how to advocate for adjustments) makes the difference between HRT that partially helps and HRT that reliably works.

The Three-Month Review

The three-month review is standard clinical practice after starting HRT and is recommended by NICE guideline NG23.[1] Its purpose is to assess:

  • Whether vasomotor and other symptoms have improved, and by how much
  • Whether side effects experienced in the adjustment period have resolved
  • Whether the current dose is adequate or whether a dose increase is warranted
  • Whether any unexpected symptoms have emerged

The most common outcome of a three-month review is a dose increase. Starting doses for transdermal estradiol (typically 25 to 50 mcg patch, or equivalent gel/spray) are conservative. Many women need 75 to 100 mcg of transdermal estradiol, or the equivalent, for adequate symptom control. Inadequate symptom control at three months is usually a dose issue rather than evidence that HRT is not appropriate.

If the three-month review is not proactively offered by your practice, request one. At the appointment, describe specifically which symptoms have improved, which have not, and the degree of change, rather than a general "it's better" or "it's not working." That specificity gives your prescriber the information to make targeted adjustments.

What "Adequate Control" Means

There is no universal threshold for what constitutes good symptom control, since individual experience and tolerability vary. A useful clinical benchmark: symptoms should be sufficiently reduced that they are not significantly interfering with sleep, work performance, mood, or quality of life. Occasional mild symptoms on some days are not a failure; daily significant vasomotor episodes despite HRT, or persistent sleep disruption despite adequate estrogen, indicate the regimen needs review.

The prescriber should not use "some improvement" as a reason to leave an inadequate dose unchanged. The goal is good symptom control, not just partial improvement.

Dose Titration for Transdermal Estrogen

Transdermal estradiol doses typically step up in the following increments:

  • 25 mcg patch (or gel/spray equivalent): starting dose for most
  • 50 mcg: standard effective dose for many women
  • 75 mcg: may be required for adequate control, particularly in early perimenopause when estrogen levels fluctuate more
  • 100 mcg: upper end of the standard prescribing range; appropriate for women with significant symptoms not controlled at lower doses
  • Above 100 mcg: occasionally used in specialist settings for surgical menopause or specific circumstances

For gels, equivalent doses vary by product (Oestrogel, Sandrena, Lenzetto spray all have different dosing conventions). Prescribers should match dose by estradiol content, not by number of pumps across different products.

Dose increases should be tried for a minimum of 6 to 8 weeks before concluding a higher dose is not effective, since it takes time for tissue response to catch up with circulating levels.

Progestogen Adjustment

For women with a uterus, progestogen must be included in HRT to protect the endometrium. The most common reason for progestogen adjustment is mood symptoms. If the progestogen phase (in cyclical regimens) or continuous low-dose progestogen is causing irritability, depression, bloating, or PMT-like symptoms, the options are:

Switch from synthetic progestin to micronized progesterone. Synthetic progestins (norethisterone, medroxyprogesterone acetate, levonorgestrel) have different receptor binding profiles and are more likely to cause mood symptoms than micronized progesterone (Utrogestan, Prometrium), which converts to allopregnanolone and has a GABAergic calming effect. Many women who experience significant mood symptoms on a synthetic progestin tolerate micronized progesterone well.

Switch from cyclical to continuous progestogen. Cyclical progestogen regimens produce a withdrawal bleed and a monthly hormonal variation that some women find destabilising. Continuous combined HRT (continuous estrogen plus continuous low-dose progestogen) removes the cyclic variation. It is appropriate in women who have been postmenopausal for more than a year, or in those who prefer no bleeding.

Adjust the dose or schedule of progestogen. Some women tolerate progestogen better taken at a different time of day. Many find bedtime dosing of micronized progesterone better tolerated, since its sedative GABAergic effect becomes a benefit rather than a burden.

Bleeding on HRT

Cyclical regimens are designed to produce a regular withdrawal bleed. This bleed should be predictable, arriving at approximately the same time in each cycle, and should not be heavy or painful. Irregular bleeding, unpredictable timing, or heavy withdrawal bleeds warrant clinical review.

Continuous combined regimens are designed to produce no bleeding once the endometrium has become atrophied under continuous progestogen. Irregular spotting and light bleeding is expected and normal in the first 3 to 6 months of continuous HRT. Bleeding that persists beyond 6 months, recurs after a period of amenorrhoea, or is heavy at any point should be investigated to exclude endometrial pathology. This typically means a transvaginal ultrasound to assess endometrial thickness, and sometimes endometrial biopsy.

Any postmenopausal bleeding (defined as bleeding occurring more than 12 months after the last natural period, in a woman not on HRT or on continuous combined HRT) must be investigated to exclude endometrial cancer, regardless of HRT use. No exceptions.

Annual Review

After the initial period of adjustment, NICE recommends an annual HRT review.[1] This should cover:

Symptom control. Are symptoms still adequately managed? Symptoms can change over time: some women need less estrogen as they move further from the menopause transition and symptoms naturally diminish; others need a dose increase as the body's endogenous estrogen production decreases further.

Bleeding pattern. Relevant for women on cyclical HRT transitioning to continuous, or any changes in bleeding pattern on existing regimens.

Blood pressure. Transdermal estrogen does not raise blood pressure, but oral estrogen may in susceptible women. Blood pressure monitoring at annual review is appropriate for all women on HRT.

Cardiovascular risk. Women over 60, or those on HRT for more than 10 years, warrant assessment of cardiovascular risk factors (cholesterol, blood pressure, glucose, BMI, smoking status). This does not mean HRT should be stopped; it means a conversation about risk-benefit in light of current health status.

Breast health. Annual review is an opportunity to confirm mammography screening is up to date. In England, routine NHS breast screening runs from age 50 to 70 on a 3-yearly schedule. Women on HRT should ensure they are on the screening register and attending.

Bone health. Women on HRT long-term for symptom control are also receiving bone protection as a secondary benefit. Women who stop HRT and have risk factors for osteoporosis may need a DXA scan to determine whether pharmacological bone protection is needed.

Libido and sexual function. Often not proactively asked about. If sexual function is not adequately addressed by current HRT, testosterone supplementation may be appropriate to raise at annual review.

When HRT Is Not Working

If symptoms remain poorly controlled despite dose titration, several possibilities should be considered:

Absorption issues. Some women absorb transdermal estradiol less efficiently through skin, due to individual variation in skin thickness, application site, or concurrent skincare products. Switching to a different application site, avoiding applying emollients to the same area, or switching to a different transdermal formulation (e.g. from patch to gel) may improve absorption. Blood estradiol levels can be measured to confirm whether the dose is actually producing therapeutic levels, though this is a clinical decision rather than routine practice.

Concurrent thyroid disease. Hypothyroidism produces symptoms that overlap substantially with perimenopausal symptoms. If HRT is not controlling symptoms, checking thyroid function is appropriate to exclude an untreated concurrent condition.

Inadequate testosterone. Fatigue, low mood, and low libido may persist on estrogen-only regimens if testosterone deficiency is also present. Worth raising explicitly if these symptoms are prominent.

Psychological contributors. Sleep disruption, anxiety, and depression can maintain symptom burden independently of estrogen levels. If vasomotor symptoms are well controlled but sleep, mood, and cognitive symptoms persist, these may require specific assessment and treatment in addition to HRT.

Routine Blood Tests

Hormone levels (estradiol, FSH) are not routinely measured during HRT monitoring except in specific circumstances: suspected absorption issues, transition from one formulation to another, or surgical menopause requiring physiological replacement confirmation. Clinical response (symptom control and side effect profile) is the primary guide to dose adjustment, not the blood level.

References

[1] National Institute for Health and Care Excellence. (2015, updated 2019). Menopause: Diagnosis and management (NICE guideline NG23). NICE. https://www.nice.org.uk/guidance/ng23