When starting Estrogel Pro (or any form of MHT) regardless of age it is best to start with a low dose to minimise short term side effects such as bloating, breast tenderness and breakthrough bleeding. Review after about 6 weeks and adjust the estrogen dose as required.

With specific reference to Estrogel Pro, I usually start patients on 1 or 2 actuations of Estrogel per day and, for women with a uterus, combine this with 200 mg Prometrium for 12-14 days per month in perimenopausal women or 100 mg Prometrium daily for post-menopausal women. I would use a higher dose of Estrogel for women with premature ovarian insufficiency.

Current recommendations are that MHT can be continued for as long as is consistent with your treatment goals. Of course, we recommend initiating MHT within 10 years of the LMP but, if a woman has been on MHT for some years and then turns 60, 61 and so on, that, in itself, is no reason why she should stop treatment if she is symptomatic.

A useful approach is to advise your patients to have a short break from their MHT for a few weeks BEFORE seeing you for their annual review. That gives the patient an opportunity to assess whether or not symptoms have returned and thus a need to continue therapy.

With specific regard to tibolone, there was one paper which reported an increased incidence of stroke, but this was in older women who were average age of about 64 years when they INITIATED therapy which is a different proposition to continuing therapy at that age.  A systematic review and meta-analysis in 2019 (Vinogradova 2019) found no increase in thromboembolic risk for users of tibolone.

Yes. 1 pump of Estrogel is equivalent to 1mg oral estradiol valerate or 25 μg patch. 2 pumps is equal to 2 mg oral estradiol valerate or 50 μg patch, which are the bone-sparing doses of commonly-used preparations.  Both doses have been shown to improve bone density at the lumbar spine, the hip and other sites, and thus reduce the risk of osteoporosis by the same magnitude as other non-hormonal bone sparing agents, however there will be significantly more individual non-responders with 1 pump of Estrogel compared with 2 pumps. MHT is an excellent treatment for bone health when initiated in women within 10 years of their LMP.

Estrogel is rapidly absorbed through the skin and an application will be dry within 5 minutes.  Wiping of the application site 5 minutes after application removed 1% of the dose in clinical trials.

It is recommended that patients wash their hands after application. A clinical trial using 15 minutes of direct skin to skin contact 1 hour after application as a marker found no significant transfer of estrogen between treated and untreated subject. It is recommended direct skin contact be avoided for 1 hour after application.

The question of how to treat women with a history of endometriosis is complex.

Firstly, for early-stage endometriosis where the surgeon is confident all endometrial tissue has been removed surgically, estrogen only therapy may be acceptable.

For women with advanced stage disease who have undergone a pelvic clearance the risk of recurrence is about 3-4%. Good data on ‘best treatment’ is lacking but systematic reviews have concluded that estrogen only therapy is associated with the highest risk of recurrence (3-4%) and that continuous combined therapy is associated with minimum risk of recurrence. (Gemmell 2017).

Factors to consider within this treatment plan include patient co-morbidities, age at which the surgery occurred, time between surgery and commencement of MHT, tolerance of progestogen component etc. which will all impact on a decision on when, if at all, to convert to estrogen only therapy.

Yes there is data from a RCT back in 1996 (PEPI 1996) which shows that 100mg progesterone daily or 200mg daily for 12-14 days per month over 3 years resulted in no change from placebo levels for any and all forms of endometrial hyperplasia.

There is very limited data on how much progesterone is required when using 4 actuations of Estrogel (or, for example, a 100 μg patch). The current recommendation is to use the same progesterone dose as for lower Estrogel doses. If you are using the sequential regimen, regular on time withdrawal bleeds will provide reassurance. If you are using continuous 100mg daily progesterone, then amenorrhoea will also provide reassurance.

If irregular bleeding occurs in either case (after the usual settling in period of 4-6 months) I would advise a good quality TV Ultrasound to assess endometrium (if on sequential do this within 6 days of the bleed or the cycle of progesterone). Treat as always if endometrium is > 4mm otherwise consider 200mg daily for continuous users or 400mg for 12-14 days per month. The data is not strong, so this is low level guidance.

Of course, you should use the dose of Estrogel required to alleviate symptoms, not more.

Because there was one small study quite a long time ago which demonstrated that the few days off progesterone each month was associated with a lower risk of spotting and breakthrough bleeding. I think you need to weigh that benefit up against issues of compliance associated with stopping and starting.

Most women find the progesterone effect at night helps them sleep rather than puts them to sleep but I would advise each woman to assess how much this affects them individually.  If she were a busy on call obstetrician, it might be a problem!  She could also try progesterone in the morning to assess the effect (at a suitable time). Not all women experience sedation. The most important point is not to take the progesterone immediately after a meal as the food facilitates rapid absorption and thus a more rapid onset of drowsiness. It doesn’t matter whether or not it is taken half an hour, 1 hour or 1 minute before bed otherwise.

All progestogens are metabolised in the liver. Because of the hepatic pathway, oral hormones should not be given to anyone with acutely abnormal liver function.

The effect of progesterone of lipid metabolism is less than that seen with synthetics. There is no effect on glucose metabolism. I could find no other specific evidence of other different effects of progesterone over synthetic progestins on liver function.

High breast density is a risk factor for breast cancer. Systemic estrogens will potentially increase mammographic density above baseline so I would always make sure the patient had an up to date mammogram before prescribing.

Body identical MHT is not contraindicated in this patient but it would be wise to start with the lowest possible dose. Research has shown that combination body identical MHT reduces breast cell proliferation and increases breast cell apoptosis more than estrogen alone or estrogen plus medroxyprogesterone acetate (MPA) (Courtin 2012).

With this patient there are several important steps to take. 1. you must first attempt to identify the cause of the PE particularly If there was a cause unrelated to hormones (e.g. MVA, post-surgery, cancer etc), related to hormones (e.g. OCP use) or unexplained.  Try to ascertain if screening for a thrombophilia has been performed and, if not, arrange those tests. 2. When was the PE?  If the patient suffered the PE a number of years prior to her presentation with POI, you can be further reassured.

Research has shown that in patients with a single prothrombotic mutation, relative risk of VTE is approximately 4 and that this risk is not increased by transdermal estrogens (Straczek 2005) although risk is increased by oral estrogens. Risk of VTE is not increased by transdermal estrogens in normal post-menopausal women (Vinogradova 2019) nor in obese women (Canonico 2007).

Transdermal MHT will not increase risk of subsequent VTE for women who have a history of DVT after fracture or surgery.

Yes, focal migraines are not a contraindication to MHT.  Transdermals should be used to provide the most stable levels of serum estradiol thus minimising the risk of migraine associated with fluctuating hormone levels.

Data is inconclusive.  One study by Harden et al. reported an increased seizure frequency amongst women taking CEE and MPA.  Once again transdermal low dose continuous combined therapy would seem to offer the best chance of symptom relief with minimal risk of seizures.

Women who are still feeding often experience hot flushes because their endogenous estrogen levels are low. If those levels are increased it will to some extent suppress lactation. Once breast feeding is well established (say > 6 months) supplementary estrogen could be given if the woman has premature ovarian insufficiency but it is not appropriate to give systemic estrogens to non-menopausal lactating women.

Data on the effect of Mirena IUCD and breast cancer risk is mixed. The theoretical argument is that levonorgestrel (LNG) binds to estrogen receptors. It is worth remembering that serum levels of LNG are about the same as those seen with progestin only birth control pills which have never been linked to increased risk of breast cancer.

A review of recent data noted that although a Danish registry-based study reported an increased risk of breast cancer (RR 1.21, 95% CI 1.11 to 1.33) (Morch 2017) other data differed (Samson 2016, Westhoff 2018). A study of 5113 women from Germany and Finland found no increased risk but was unable to adjust for other risk factors except age (Dinger 2011). A smaller Israeli study also found no increased risk with the same caveats regarding confounders (Siegelmann-Danieli 2018).

Mirena has been shown to provide endometrial protection for women having normal reproductive ovarian function. The doses of estrogen used in MHT are less than those seen in normal menstrual; cycles (averages). Mirena is an accepted source of progestogen for use in MHT for the usual duration of that device – 5 years. It should be noted that unexpected post-menopausal bleeding must always be investigated and that reducing risk of endometrial cancer to baseline does not mean there is no risk.

Duavive is a combined MHT using conjugated estrogens 0.45mg plus bazedoxifene 20mg daily. Bazedoxifene is a SERM with anti estrogenic properties in the endometrium and breast.  The combined therapy has been shown to alleviate vasomotor symptoms in post-menopausal women, to provide endometrial protection in those doses, to improve bone density and the lumbar spine and hip and not to increase mammographic density.  It is a useful form of low dose oral MHT for post-menopausal women.

The risk of VTE may vary depending on dose of transdermal estrogen. Early data from the UK GP Data base suggested that doses of transdermal estrogen above 50 μg may be associated with increased VTE risk. However, a systematic review and meta-analysis (Vinogradova 2019) found no increased VTE risk for any dose of transdermal estrogen.

The only alternative to estrogen patches or Estalis patches is an estrogen gel such as Estrogel or Sandrena (estradiol) combined with a progestogen when necessary.  The most economical approach would be to prescribe EstrogelPro for such women using a dose of 2 pumps of Estrogel daily plus one 100mg Prometrium capsule each night

If by topical estrogen you mean estrogen used in the vagina for local symptoms, the answer is that topical estrogens used every day for 2 weeks then twice weekly do no affect cardiovascular breast or VTE risk in any way.

If you are using topical estrogen therapy in the approved dose initially daily for 2 weeks then twice weekly thereafter there is no need for any supplementary progestogen because the risk of endometrial hyperplasia is not increased.

Topical estrogens may be used for vaginal dryness and dyspareunia in breast feeding women.  The levels of estriol or estradiol in serum are trivial and will not affect lactation.

Implanon may be theoretically effective for endometrial protection in women using MHT but it has never been subjected to appropriate clinical trials and is not recommended for this indication (UK FSMH guideline).

Endometrial polyps are focal areas of overactive endometrium and may often exhibit features of endometrial hyperplasia. For that reason, it is generally recommended that they be removed.

The prevalence of asymptomatic polyps in post-menopausal women is estimated to range between 13-50%. The majority are benign. Malignant pathology is seen in up to 4.8% of cases. In a Canadian guideline (Wolfman 2018) advice was that when deciding to remove a polyp in an asymptomatic woman consideration should be given to size (>5mm) and patient age (>60) as well as underlying risk factors for endometrial cancer and, of course, surgery.

There is no evidence to suggest short term use of topical vaginal estrogens would alter risk of endometrial cancer.