What will happen the first time I visit an HRT clinic?

All doctors and clinics have their own individual approach but our clinic would be fairly typical.

We find it helpful for our patients to complete a brief questionnaire before consultation. This is designed to provide us with an overview of your symptoms and your expectations should you elect to start HRT.

Details of any family history of heart, bone, DVT / pulmonary embolism, or breast disease are recorded. General and pelvic examinations are important to reassure you that there are no physical problems.

There is always a choice of treatment. We discuss the potential benefits and possible problems of HRT in general and for you as an individual in particular. Each patient receives an information leaflet. If a patient is uncertain as to how she wishes to proceed we suggest that she returns in about four weeks.

How can atrophic vaginitis - dry vagina at menopause - painful sex - be treated?

What is atrophic vaginitis?

Atrophy is the partial or complete wasting away of body tissue and what is vaginitis? Vaginitis is inflammation of the vagina.

What local genital symptoms might be associated with the menopause?

After the menopause, as a result of vaginal atrophy due to loss of estrogen, vaginal dryness and discomfort are more likely to become a problem for you. Local infection, atrophic vaginitis, becomes more common now that there is less protective lactic acid and this may result in inflammation causing soreness and discharge. The vaginal dryness and inflammation may cause discomfort or even pain when you make love (dyspareunia). On occasion, the inflammation may cause bleeding. All postmenopausal bleeding must be investigated (17).

The peri menopause symptoms associated with atrophic vaginitis are:-

  • Genital  Dryness
  • Itching
  • Burning
  • Dyspareunia - Painful Sex
  • Burning leukorrhea
  • Vulvar pruritus
  • Feeling of pressure
  • Yellow malodorous discharge
  • Urinary :-

  • Dysuria
  • Hematuria
  • Urinary Frequency
  • Urinary tract infection
  • Stress incontinence

These atrophic vaginitis symptoms can occur as pre menopause symptoms although they are more common in post menopausal women.

How can atrophic vaginitis - dry vagina at menopause - painful sex - be treated?

Topical oestrogen (creams and pessaries) are commonly used in postmenopausal women to improve the quality of the vaginal epithelium in atrophic vaginitis. Fifteen percent of premenopausal women, 10-40% of postmenopausal women, and 10-25% of women receiving systemic hormone therapy experience urogenital atrophy. The most common symptoms are dryness, burning, pruritus, irritation, and dyspareunia (painful sexual intercourse). Topical Estrogen or hormone replacement therapy (ERT-HRT) is the treatment of choice in postmenopausal women.0101

If genital symptoms, such as vaginal dryness, pain during lovemaking or perhaps bladder symptoms are troubling you, these could be due to reduced oestrogen levels in the tissues around the genital area. These symptoms usually respond to HRT or to topical preparations (oestrogen creams or pessaries). On occasion, local symptoms may fail to respond to HRT anyway and additional topical oestrogen may be required. To begin with, the creams or pessaries are introduced each night for ten days to two weeks and then reduced to a maintenance regime varying from twice weekly to perhaps no more than once each month depending on symptoms, age and response. There are a variety of topical oestrogen preparations (Table 28.1).

Estring (Pharmacia and Upjohn), a synthetic soft rubber ring which slowly releases oestradiol can be introduced into the vagina and replaced at three monthly intervals. If the uterus is still present intermittent courses of progestogen should be considered to encourage endometrial shedding (HRT and progestogen). The ring is as effective as oestrogen creams and some women find the ring more acceptable.

 


Table 28.1 Topical creams and pessaries that are commonly used in menopause treatment.

Preparation

Oestrogen

Company

Ortho-Gynest Pessaries

Oestriol 500 g

Janssen-Cilag

Ortho-Gynest Cream

Oestriol  0.01%

Janssen-Cilag

Ovestin Cream

Oestriol 0.1%

Organon

Ovestin Pessaries

Oestradiol 1mg

Organon

Premarin  Cream

Conjugated oestrogens 625 mg

Wyeth

Vagifem Pessaries

Oestradiol 25 microg

Novo Nordisk

Estring Ring

Oestradiol (7.5 microg release/day)

Pharmacia and Upjohn

Almost invariably, unless you are taking HRT, there will be some degree of vaginal atrophy after the menopause. Quite frequently, patients are referred with vaginal discomfort and a physical examination reveals a prolapse (1). The only way to determine how much of the discomfort is due to the vaginal atrophy and how much to the prolapse is to treat the atrophy with topical (local cream or pessary) oestrogen and then reassess the symptoms.

 

How do we decide which will be the most appropriate HRT for me?


Figure 28.1

Figure 28.1 is a flowchart indicating the salient questions to be addressed when considering the HRT options. There are three main questions leading to the appropriate options:

First, have you had a hysterectomy ?

If your womb has been removed (hysterectomy), oestrogen replacement can be prescribed alone; there is generally no need for progestogens. If the womb has not been removed and oestrogen were prescribed unopposed, there would be a chance of the endometrium (womb lining) becoming unduly thickened with a risk of bleeding problems and on rare occasions malignancy (HRT and progestogen).?

Secondly, if your womb is still present, are you still seeing your periods?

If periods are occurring spontaneously HRT would be supplementing the natural hormone cycle. In addition to the oestrogen replacement your doctor would suggest a progestogen for 10 to 12 days each month to ensure a regular withdrawal bleed. This prevents your endometrium (lining of the womb) becoming too thick. If you have not reached your menopause and a non-bleed variety of HRT were prescribed you would almost certainly have irregular bleeding.

Finally, if your womb is still present and the menopause has already occurred, do you wish to have a regular withdrawal bleed?

There is a choice of prescribing the progestogen sequentially to produce a regular withdrawal bleed or prescribing the progestogen on a daily (non-cyclical) regimen: This continuous combined HRT provides the benefits of HRT without “periods". A blood hormone test can be arranged to provide a guide as to whether you have reached your menopause ( 14).

 

What side effects could I experience when I start HRT?

You will probably have no difficulties as hormone replacement therapy is simply ‘replacing’ a natural hormone deficiency.

  • You may experience mastalgia (breast discomfort) initially but this usually settles quickly by itself or with pyridoxine (vitamin B6) 50mg twice daily or gamolenic acid up to 320 mg daily.
  • If you have not had a hysterectomy , there may be a little spotting of blood during the first month or so.
  • Around the menopause, there is a tendency to gain weight, whether you take HRT or not (Q 28.22).

What is the choice of oestrogen only preparations?

Oestrogens may be natural or synthetic although both may be manufactured.

When natural oestrogens are taken, the oestrogens in the blood are the same as would be released by the ovaries. Hormone replacement uses natural oestrogens.

After synthetic oestrogen administration, oestrogens structurally different from those released by the ovaries appear in the blood. Ethinyl oestradiol and mestranol are synthetic oestrogens used in combined oral contraceptive pills.

Estrogen Only HRT Preparations

There are several estrogen only HRT preparations. The oestrogen can be administered

  • orally (tablets –Table 28.2),
  • transdermally (patches –Table 28.3 and Table 28.4 or gels),
  • subcutaneously as implants (Figure 28.1),

The nasal spray and vaginal ring methods have been introduced in 2001 but they were discontinued in 2006.

Table: 28. 2 Estrogen Only Tablets

PREPARATION

OESTROGEN

DOSE (mg)

COMPANY

Climaval

Oestradiol valerate

1 and 2

Novartis

Elleste Solo

Oestradiol

1 and 2

Searle

Harmogen

Oestrone

1.5

Pharmacia and Upjohn

Hormonin

Oestriol/Oestrone/

oestradiol

0.27/1.4/

0.6

Shire

Premarin

Conjugated Oestrogens

0.625 and 1.25

Wyeth

Progynova

Oestradiol valerate

1 and 2

Schering

Zumenon

Oestradiol

1 and 2

Solvay

Doctors tend to have their personal preference for first choice recommendation. As with the combined oral contraceptive pill, the acceptability and side effects for each preparation vary between patients. If you have had a recommendation from a friend or relative it would seem sensible for you to try it.

Premarin is derived from pregnant mares urine. It has been popular for many years and much of the research on HRT relates to this product. The pharmaceutical company producing Premarin has documented evidence from veterinary surgeons that there is no cruelty to the animals involved.

Women who have been deprived of oestrogen for more than a few months seem to be prone to side effects and in particular to mastalgia (breast discomfort). It is often wise, particularly if there is a history of mastalgia, to begin with a low dose preparation; the tablets can be taken every few days and gradually increased to the daily regimen.

Oestrogen tablets are broken down in the small bowel where the oestrogen is absorbed. The blood circulating through the bowel then passes to the liver where much is broken down before it has a chance to reach the rest of the body. Sometimes side effects associated with oestrogen tablets may be avoided by using skin patches or by introducing the oestradiol as an implant under the skin. Blood from the skin passes to all parts of the body and not specifically through the liver on its first-pass. Several companies produce patches of different strengths designed to release between 25 and 100 ug (micrograms)/24 hours. Most must be changed twice each week (Table 28.3).

HRT Patches


Table 28. 3 Oestradiol skin patches.

PREPARATION

DOSE (mg / 24 hours)

COMPANY

Elleste Solo MX

40 or 80

Searle

Estraderm MX

25, 50, 75 or 100

Ciba

Estraderm TTS

25, 50, or 100

Ciba

Evorel

25, 50, 75 or 100

Janssen-Cilag

Fematrix

40 or 80

Solvay

Menorest

37.5, 50 or 75

Poulenc Rorer

 

Some patches are designed to be changed at weekly intervals:


Table 28. 4 

PREPARATION

DOSE micg / 24 hours)

COMPANY

FemSeven

50, 75 or 100

Merck

Progynova TS

50 or 100

Schering

Some women find that their patches stay in place whilst bathing but most prefer to take the patch off and replace it afterwards. Allergic reactions resulting in irritation and redness can be a problem although the more recent patches seem less likely to cause this.

There are two oestrogen gels (Oestrogel: Hoechst and Sandrena: Organon) for application to the skin. Between two and four measures of Oestrogel are rubbed gently into the upper arms, shoulders or thighs daily usually after bathing. Sandrena comes in 0.5 and 1mg sachets, and the gel is similarly applied each day.


Related Medical Abstracts - Click on the paper title:-

 

How are oestradiol implants introduced?


Before hysterectomy, if the ovaries are to be removed, most patients would be offered a subcutaneous (under the skin) oestradiol implant.

    • Subsequently, these implants are introduced on an outpatient basis under local anaesthetic.
    • A half-inch incision is required and a small tube is introduced under the skin.
    • The implant is then inserted down the tube.
    • The wound may require one or two stitches.
    • We generally make the small incision low down on the abdominal wall but some prefer them high and to the side of the buttock area.
    • They may be introduced at between six- and twelve-month intervals.
    • The oestradiol implants are available in 25, 50 and 100mg pellets, the largest being the size of an airgun pellet which are few millimetres long.

    Figures showing insertion of oestradiol implant.

     

Is it possible to be given too much oestrogen?

This cannot occur if tablets, gels or patches are used according to the recommended doses.

Occasionally, there can be problems with implants. Implants may continue to release oestradiol for eighteen months or more. There is a wide variation in serum (blood) oestradiol levels following an implant. In one study, the range was between 114 and 853 pmol/l one year after a 100mg oestradiol implant.

Some patients seem to require implants relatively frequently to control their menopausal symptoms and this could result in blood levels above those experienced naturally during years when the ovaries are functioning.

If it is suspected that your blood oestradiol level could be running high although you feel that you need another implant a blood sample can be analysed.

At one time, if the blood oestradiol level proved to be high, the term tachyphylaxis was used although tachyphylaxis strictly means that symptoms seem inappropriate for normal blood levels. We now assume that the symptoms must be related to the rate of fall of oestradiol levels rather than oestrogen deficiency. In these circumstances, a 25 mg oestradiol implant can be introduced or a low dose oral preparation or transdermal patch used to relieve symptoms whilst the original implants gradually lose their activity.


Related Medical Abstracts - Click on the paper title:-

How long will my oestradiol implant last?

This varies from patient to patient and the strength of the implant used.

A fifty eight year old lady had her last of several oestradiol implants in 1994. She had found the implants suited her best. As she had not had a hysterectomy cyclical progestogens were required to prevent problems with the endometrium (HRT and progestogen). She then decided that she would prefer to avoid regular bleeds. We have monitored her oestrogen levels and it has taken four years for this to fall to a level where we can safely consider her for a continuous combined preparation. In our experience it is unusual for implants to function for so long.

Why might I need progestogen in addition to oestrogen replacement?

If your uterus is present, progestogen is essential to protect the lining of the womb from undue thickening (hyperplasia) by the oestrogen in HRT and the potential for malignant change.

Progestogen almost completely prevents the risks of malignancy. It has been shown that if you take oestrogen replacement therapy together with progestogen, you are even less likely to develop cancer of the endometrium than a lady who has never been on HRT.

Many women who have not yet reached the menopause experience symptom relief with HRT. In general, progestogens are prescribed for ten or twelve days on a sequential basis. A withdrawal (period-like) bleed usually occurs about 2 to 4 days after the progestogen course has been completed. As with the combined pill, the withdrawal bleed with HRT should replace your period and would not be in addition to it.

The choice includes

  • a combination of an oestrogen preparation (Figure 28.1 Group A) with a progestogen (Group B),
  • or a combination pack with the oestrogen and sequential progestogen (Group C).

Two progestogens have been marketed specifically for combination with an oestrogen. These are

  • Micronor HRT (norethisterone 1mg – Janssen-Cilag) and
  • Duphaston HRT (Dydrogesterone 10mg - Solvay).

It must be emphasised that these are to be used in combination with an oestrogen – they are not in themselves forms of HRT.

Progesterone gel (Crinone - Serono) can be introduced vaginally every other night from the 15th to the 25th day of the cycle. There are two strengths – 4% and 8%.