Introduction

Hormone implants as replacement therapy for the menopause have been in use for over 40 years. These guidelines are issued to help medical practitioners. They are therefore guidelines rather than rules.

Most practitioners in this field develop their own particular strategies and may have varying views for example on the levels of E2, which they choose for timing repeat implants.

There is a great deal of variability between laboratories in oestradiol assay results. Your local pathologist should inform you about the specificity of their assay. It is generally better to use the same laboratory for each patient.

 The AMS Practitioners Guidelines for Oestradiol (E2) Implants 298.98 Kb

Important Points

• Implants are less commonly used currently due to the increased choice of other hormonal preparations and could be considered as "second- line" therapy in women unable to tolerate other forms of HRT.
• 50mg oestradiol implants at approximately 6 monthly intervals preceded by E2 measurement are generally well tolerated and efficient.
• Implants are best suited for the hysterectomised woman.  If the uterus is intact a   progestogen must be added.  The difficulty arises in knowing when to cease the progestogen (if continuous) after the last implant and a continuing withdrawal bleed can be helpful in this instance- our record is 3 years after the last implant!!
• Implants need to be implanted deeply into the subcutaneous fat.
• Tachyphylaxis can occur with all dosages and is more common with repeated implants.
• Regular screening mammography is essential in management of all women on hormone replacement therapy including implants.

Indications

• These include the usual indications for any hormone replacement therapy (see AMS Combined HRT and Oestrogen only HRT.)
• For women who complain of moderate to severe loss of libido, a testosterone implant may be effective when used in conjunction with oestradiol. (see AMS Low libido and Testosterone therapy.)
• Implants are of particular value in women who have had a hysterectomy and cannot tolerate other forms of therapy (NB: If they can't remember to take an oestrogen you may not be able to rely on them to take a progestogen.) They are not contra-indicated in the woman with an intact uterus, but progestogens will be required for endometrial protection. Bleeding problems may be encountered even when given cyclically, because of the maintenance of relatively high oestradiol levels. 
• A progesterone-releasing intra-uterine device may also be used for endometrial protection although there is very little data available regarding this indication at present.

If a woman decides to stop using implants progestogens should be continued until withdrawal bleeding ceases, as oestrogenic activity sufficient to produce endometrial hyperplasia may continue up to 2 - 3 years after the last implant.

Site of Insertion

• Lower abdomen, buttocks (or rarely, thigh) - preferably into a fat pad and not into scar tissue.
• Effective absorption of the implant may be hindered by fibrous encapsulation if not implanted into fat. Hence, a new insertion site should be used each time.
• Dosage: 20mg, 50mg and 100mg pellets.
   20mg will last 2-4 months
   50mg will last 4-8 months
  100mg will last 8-12 months
• Implants may remain active for longer than this - and E2 levels should be measured prior to insertion of the next implant. It is recommended that another implant is not inserted until women are symptomatic and have a satisfactory E level.
• The recommended dose is 50mg oestradiol implant every 6 months. Most patients respond adequately to this dose.
• The 20mg implant is not often used for long term management. It is sometimes used as a "test" dose to test oestrogen sensitivity since its action will wear off in 2 - 4 months. This is important if significant side effects such as mastalgia are predicted.

Measurement of Plasma Oestradiol (E2)

Plasma oestradiol should be measured before all implants due to the problem of tachyphylaxis. Symptoms of hypo-oestrogenicity are not a sufficient guide. Do not insert another implant until levels fall below 400 pmols/litre.

If there is doubt about the activity of an implant, measurement of the E2 level at 2 - 4 weekly intervals may help in clinical management.  Be guided also by the patient's symptoms eg: return of hot flushes, increasing tiredness.

Tachyphylaxis

• This poorly understood phenomenon may occur with implant therapy where some women experience withdrawal symptoms despite E2 levels being adequate. It is more likely to occur if implants have been inserted too frequently before E2 levels fall. Management is difficult and usually relies on the use of short acting transdermal oestrogen preparations to alleviate the symptoms until the oestrogen levels return to acceptable levels. Continued implants should be avoided if tachyphylaxis occurs.
• Monitoring of plasma oestradiol levels is particularly helpful if symptoms are recurring sooner than expected. Do not insert another implant until levels fall below 400 pmols/litre..

Levels of E2 at which Implants are advisable.

• Most women feel well with E2 levels between 300 and 600 pmols/litre but there is great individual variation.
• Even the experts disagree about the desired upper level at which new implants should be inserted - 350 pmols/litre or 400 pmols/litre are thought appropriate by some. Others feel that 600 pmols/litre is the level below which many women start to get symptoms of oestrogen withdrawal.   

Dealing with problems

• Encapsulation - an implant may be felt just under the skin - having been inserted cutaneously instead of deep into the fat layer. It usually does not function in this site and may be removed if palpable or tender (it is usually easy to do this).
• Haematoma - at time of insertion; prevention is best - pressure over the site, insertion of one or two skin sutures if necessary. It does not cause trouble or loss of function unless it is unusually large or becomes infected.
• Spontaneous extrusion of an oestradiol pellet is uncommon. 
• Removal of implant - may be necessary if side effects such as breast pain and engorgement are insufferable. The implant can be difficult to locate even with the use of ultrasound localisation. Patients should be counselled regarding this prior to insertion. Implants are ideally implanted deep into fat.  This may make retrieval difficult. Rarely one has to do a small lipectomy to remove the pellet.

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Content Updated 7 October, 2008