Which HRT?- Chapter 28: - Womens Health

Contents

1 Q 28. 1 What happens when I visit my doctor / HRT clinic for the first time?
2 Q 28. 2 How can local genital symptoms such as vaginal dryness be treated?
3 Q 28. 3 How will we decide which is the most appropriate HRT / Hormone Replacement Therapy preparation for me?
4 Q 28. 4 What problems might occur when I start HRT?
5 Q 28. 5 What is the choice of oestrogen-only HRT preparations?
6 Q 28. 6 How are oestradiol implants introduced?
7 Q 28. 7 Is it possible for me to be given too much oestrogen?
8 Q 28. 8 How long will my oestradiol implant last?
9 Q 28. 09 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?
10 Q 28. 10 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?
11 Q 28. 11 Could we adjust the timing of the withdrawal bleed associated with sequential (cyclical progestogen) HRT preparations for my social convenience?
12 Q 28. 12 I have gone through the menopause. Does HRT – Hormone Replaement Therapy – mean that I must have ‘periods’ again?
13 Q 28. 13 What is tibolone (Livial – Organon)?
14 Q 28. 14 I have had a premature menopause. What forms of HRT are available?
15 Q 28. 15 Is there an indication for the levonorgestrel intrauterine system (Mirena) in the management of the menopause?
16 Q 28. 16 Is there a place for progesterone replacement therapy?
17 Q 28. 17 Is there a place for testosterone replacement therapy?
18 Q 28. 18 My sex drive (libido) is rather low. Is there anything that might improve it?
19 Q 28. 19 How would the possible advantages and disadvantages of HRT compare for me?
20 Q 28. 20 What side-effects could I have with HRT?
21 Q 28. 21 What can be done if I develop irregular bleeding on HRT?
22 Q 28. 22 If I start HRT – Hormone Replacement Therapy, will I gain weight?
23 Q 28. 23 If I have menopausal symptoms but I cannot take HRT what other options are available for me?
24 Q 28. 24 How will I be monitored once I start HRT?
25 Q 28. 25 For how long can I take HRT?
26 Q 28. 26 Do most women continue with HRT?
27 Q 28. 27 How can doctors encourage their patients to continue with our HRT?
28 Q 28. 28 Are women who have had higher education more likely to take HRT?
29 Q 28. 29 Are there any new developments with HRT?
30 Q 28. 30 What are your conclusions with regard to the risks and benefits of HRT?
31 Q 28. 31 Could I have some useful Web sites?

Q 28. 1 What happens when I visit my doctor / HRT clinic for the first time?

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 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.

Q 28. 19 How would the possible advantages and disadvantages of HRT compare for me?
Q 28. 20 What side-effects could I have with HRT?
Q 28. 21 What can be done if I develop irregular bleeding on HRT?
Q 28. 22 If I start HRT, will I gain weight?
Q 28. 23 If I have menopausal symptoms but I cannot take HRT what other options are available for me?
Q 28. 24 How will I be monitored once I start HRT?
Q 28. 25 How long can I take HRT?
Q 28. 26 Do most women continue with HRT?
Q 28. 27 How can doctors encourage their patients to continue with our HRT?
Q 28. 28 Are women who have had higher education more likely to take HRT?
Q 28. 29 Are there any new developments with HRT?
Q 28. 30 What are your conclusions with regard to the risks and benefits of HRT?
Q 28. 31 Could I have some useful Web sites?
Women’s Health – Home Page

Q 28. 2 How can local genital symptoms such as vaginal dryness be treated?

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 & 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 (Q28.9). The ring is as effective as oestrogen creams and some women find the ring more acceptable.

Table 28.1

Preparation

Oestrogen

Company

Ortho-Gynest Pessaries

Oestriol 500 mg

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

Tampovagan Pessaries

Stilboestrol 0.5 mg + lactic acid

Co-Pharma

Vagifem Pessaries

Oestradiol 25 mg

Novo Nordisk

Estring Ring

Oestradiol (7.5 mg release/day)

Pharmacia & 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 (Q30.1). 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.

References:

A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy (1996-1255)

Q 28. 3 How will we decide which is the most appropriate HRT / Hormone Replacement Therapy preparation for me?

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 (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 (Q28.9).

• 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 (Q26.14).

Q 28. 4 What problems might occur 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 (hysterectomy), there may be a little spotting of blood during the first month or so. Around themenopause, there is a tendency to gain weight, whether you take HRT or not (Q28.22).

Q 28. 5 What is the choice of oestrogen-only HRT 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.

There are several oestrogen 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), as a nasal spray (Aerodiol – estradiol hemihydrate – Servier) or by a vaginal ring (Menoring – estradiol acetate – Galen Ltd). The nasal spray and vaginal ring methods have been introduced in 2001.

Table:28. 2

PREPARATION

OESTROGEN

DOSE (mg)

COMPANY

Climaval

Oestradiol valerate

1 & 2

Novartis

Elleste Solo

Oestradiol

1& 2

Searle

Harmogen

Oestrone

1.5

Pharmacia & Upjohn

Hormonin

Oestriol/Oestrone/

oestradiol

0.27/1.4/

0.6

Shire

Premarin

Conjugated Oestrogens

0.625 & 1.25

Wyeth

Progynova

Oestradiol valerate

1 & 2

Schering

Zumenon

Oestradiol

1 & 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).

Table 28. 3 Oestradiol skin patches.

PREPARATION

DOSE (mg / 24 hours)

COMPANY

Dermestril

25, 50

Sanofi Winthrop

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

Rhone-Poulenc Rorer

Some patches are designed to be changed at weekly intervals:

Table 28. 4

PREPARATION

DOSE (mg / 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.

References:

New developments in topical estrogen therapy (1997-1614)

Q 28. 6 How are oestradiol implants introduced?

Before hysterectomy (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.

In our department at Whipps Cross Hospital 800 oestradiol implants are introduced each year. 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.

Q 28. 7 Is it possible for me 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.

References:

Hormone implants and tachyphylaxis. see comments

Q 28. 8 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 (Q28.9). 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.

References:

An audit of oestradiol levels and implant frequency in women undergoing subcutaneous implant therapy (1995-1186)

Q 28. 09 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?

Q 28. 10 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?

Nearly 20% of women on sequential regimens will have no bleed and the incidence increases with duration of use. The number of days of bleeding may diminish with time for those who see regular bleeds. As with the combined oral contraceptive pill (Q16.13) this is not a reason for anxiety but a variation of a normal response.

Q 28. 11 Could we adjust the timing of the withdrawal bleed associated with sequential (cyclical progestogen) HRT preparations for my social convenience?

Your doctor can usually advise you how to lengthen the cycle by delaying the progestogen component for a week or two. The packages with varying doses of oestrogen and / or progestogen do not lend themselves to this quite so readily

Q 28. 12 I have gone through the menopause. Does HRT – Hormone Replaement Therapy – mean that I must have ‘periods’ again?

Initially when it was realised that unopposed oestrogen in hormone replacement therapy (HRT) could cause problems with the endometrium, progestogens were always administered sequentially even after the menopause. The sequential regimen produced withdrawal bleeds for the majority although a few would have no bleeds. This was, no doubt, a reason for many women deciding against HRT as understandably the idea of monthly withdrawal bleeds was unacceptable for them.

With the arrival of tibolone (Q28.13; Table 28.7) it became possible to give an HRT preparation to postmenopausal women who still have their womb without causing withdrawal bleeds. Even today, many postmenopausal women are surprised to learn that they can have HRT without enduring withdrawal bleeds.

We now know that it is safe to prescribe any oral (tablets taken by mouth) HRT in combination with a low dose progestogen daily and avoid periods (Figure 28.1). There are eight tablet preparations and one transdermal patch available for ‘continuous combined’ HRT (Table 28.7) A continuous combined vaginal ring is currently being evaluated.

Table 28. 7 Continuous Combined HRT preparations.

PREPARATION

OESTROGEN/PROGESTOGEN

TABLETS

Climesse

Oestradiol valerate / Norethisterone

2 / 0.7

Elleste Duet Conti

Oestradiol / Norethisterone

2 / 1

Femoston-Conti

Oestradiol / Dydrogesterone

1 / 5

Kliofem

Oestradiol /Norethisterone Acetate

2 / 1

Kliovance

Oestradiol / Norethisterone

1 / 0.5

Livial

Tibolone

2.5

Nuvelle Continuous

Oestradiol / Norethisterone

2 / 1

Premique

Conjugated oestrogens / M.P. Acetate

0.625 / 5

PATCH

Evorel Conti

Oestradiol / Norethisterone

50/170mcg

Before themenopause, if a LNG-IUS (Mirena – Q14.26) is introduced, to provide endometrial protection for oestrogen replacement therapy, periods tend to be lighter or sometimes they stop. If you have gone through the menopause and wish to take HRT without having withdrawal bleeds and you cannot tolerate progestogens taken orally or in the patch, the LNG-IUS will provide endometrial protection and may not produce the same side-effects.

Some slight spotting of blood is common for the first few weeks and occasionally up to six months with continuous combined HRT. If this should persist or if it occurs later on, the bleeding should be reported to the doctor as investigation is required (Q24.12).

References:

Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate (1994-1163)

Q 28. 13 What is tibolone (Livial – Organon)?

Tibolone is a synthetic steroid that has progestogenic and some androgenic properties (Q2.9) as well as oestrogenic effects. As it has effects of all three groups of hormones produced by the ovaries (the female gonads) it has been called gonadomimetic. Livial has the advantages of HRT whilst allowing bleed-free HRT for postmenopausal women. There may be irregular bleeding for up to 4-6 months in 10% of patients.

References:

Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy (2001-3251)

A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms (1998-2265)

A study of the effect of tibolone on the vagina in postmenopausal women (1994-2103c)

The incidence of vaginal bleeding with tibolone treatment (1994-543)

Effect of tibolone on postmenopausal bone loss (1994-2034)

Q 28. 14 I have had a premature menopause. What forms of HRT are available?

Whereas most postmenopausal women prefer to avoid monthly bleeds, younger women may feel it more natural to see a “period” and choose to have HRT with a sequential progestogen. Assuming you still have your womb you must have a progestogen in combination with the oestrogen.

A spontaneous pregnancy is unlikely but not necessarily impossible. It must be remembered that on occasion there may yet be one or more ova (eggs) that are destined to be released at a later date (Q26.8).

Q 28. 15 Is there an indication for the levonorgestrel intrauterine system (Mirena) in the management of the menopause?

The Mirena IUS was launched in the UK in 1995 for contraception (Q14.26). For women approaching the menopause it provides excellent birth control. It provides progestogen protection of the lining of the uterus to be used in conjunction with any form of oestrogen replacement therapy (Q28.9; Figure 28.1B) whether this be by tablet, patch, gel or subcutaneous implant. Before the menopause periods, would usually be absent or light and after the menopause a Mirena would provide one option for HRT without withdrawal bleeds.

References:

The levonorgestrel intrauterine system in menopausal hormone replacement therapy: Five-year experience. (1999 – 2723)

Q 28. 16 Is there a place for progesterone replacement therapy?

Ovarian failure at the menopause is associated with cessation of progesterone production as well as oestrogen deficiency. An American physician, Dr Lee, has described and publicised his experience with ‘natural progesterone cream – ‘Progest’ – which is applied to the skin.

The progesterone is produced in the laboratory from diosgenin by extraction from the Mexican Yam. Many other reproductive hormones are similarly extracted from the Mexican Yam. A variety of clinical benefits have been claimed including increased bone density, relief of benign breast disease symptoms, enhanced libido (sex drive Q28.18) and relief of premenstrual syndrome.

Dr Lee recognises the fact that others have used progesterone in capsule form or rectal suppositories (Cyclogest) but he found that the transdermal route was more acceptable for his patients. There is some evidence that progesterone may have benefit on the heart.

Controlled studies are required to confirm the possible advantages of Progest. One recent study, at King’s College Hospital in London, found that Progest resulted in only a small increase in plasma progesterone levels and the authors commented that they were not convinced that this was likely to achieve a biological effect.

Several patients have come to me wishing to continue Progest having commenced it under the supervision of others. There have been many occasions when patients have not had their symptoms adequately controlled by oestrogen replacement therapy and Progest has apparently helped a few of them.

References:

A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women (2000-3123)

Q 28. 1 What happens when I visit my doctor / HRT clinic for the first time?
Q 28. 2 How can local genital symptoms such as vaginal dryness be treated?
Q 28. 3 How will we decide which is the most appropriate HRT preparation for me?
Q 28. 4 What problems might occur when I start HRT?
Q 28. 5 What is the choice of oestrogen-only preparations?
Q 28. 6 How are oestradiol implants introduced?
Q 28. 7 Is it possible for me to be given too much oestrogen?
Q 28. 8 How long will my oestradiol implant last?
Q 28. 9 Why might I require progestogen in addition to oestrogen?
Q 28. 10 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?
Q 28. 11 Could we adjust the timing of the withdrawal bleed associated with sequential (cyclical progestogen) HRT preparations for my social convenience?
Q 28. 12 I have gone through the menopause. Does HRT mean that I must have ‘periods’ again?
Q 28. 13 What is Tibolone (Livial – Organon)?
Q 28. 14 I have had a premature menopause? What forms of HRT are available.
Q 28. 15 Is there an indication for the levonorgestrel intrauterine system (Mirena) in the management of the menopause?
Q 28. 16 Is there a place for progesterone replacement therapy?
Q 28. 17 Is there a place for testosterone replacement therapy?
Q 28. 18 My sex drive (libido) is rather low. Is there anything that might improve it?
Q 28.18a What is the place of Viagra (sildenafil citrate) in sexual dysfunction in women?
Q 28. 19 How would the possible advantages and disadvantages of HRT compare for me?
Q 28. 20 What side-effects could I have with HRT?
Q 28. 21 What can be done if I develop irregular bleeding on HRT?
Q 28. 22 If I start HRT, will I gain weight?
Q 28. 23 If I have menopausal symptoms but I cannot take HRT what other options are available for me?
Q 28. 24 How will I be monitored once I start HRT?
Q 28. 25 How long can I take HRT?
Q 28. 26 Do most women continue with HRT?
Q 28. 27 How can doctors encourage their patients to continue with our HRT?
Q 28. 28 Are women who have had higher education more likely to take HRT?
Q 28. 29 Are there any new developments with HRT?
Q 28. 30 What are your conclusions with regard to the risks and benefits of HRT?
Q 28. 31 Could I have some useful Web sites?
Women’s Health – Home Page

Q 28. 17 Is there a place for testosterone replacement therapy?

Testosterone implants have a role for some women with reduced libido or insufficient energy when oestrogen replacement does not suffice. In one study, five aspects of sexual behaviour were monitored in three groups of women four years after hysterectomy and bilateral salpingo-oophorectomy (removal of both ovaries and the Fallopian tubes) for benign disease. One group received oestrogen replacement only, those in the second group were given a combination of oestrogen and testosterone and the third had no hormone replacement.

The rates of coitus (sexual intercourse) and orgasm were highest in the group receiving the oestrogen and testosterone. There was a relationship between the blood levels of testosterone and frequency of intercourse.

There is some evidence that tibolone (Livial) may increase libido. Tibolone is available for postmenopausal women or women who have had a hysterectomy.

References:

Androgen treatment in women [see comments]. [Review] (1999 – 3021)

Risks of menopausal androgen supplementation. (1998 – 2691)

Exogenous androgens in postmenopausal women. (1995- 2463)

The role of androgen in the maintenance of sexual functioning in oophorectomized women (1987-790)

Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause (1985-791)

Q 28. 18 My sex drive (libido) is rather low. Is there anything that might improve it?

Libido is a complex and particularly personal issue. Emotion plays a relatively major role in female sex drive and self-esteem plays a critical part in a woman’s sexual feelings. Your relationship with your partner could be encouraging or inhibiting your self-esteem. It is all too easy to get into a spiral – if your libido is low it will affect your partner and his self-esteem: he may show less interest in you thus perpetuating the underlying problem. Anti-psychotic drugs (e.g. for depression or anxiety) may be associated with reduced libido although it is difficult to quantify how much is due to the medication rather than to the underlying psychological problems.

Love-making should be one of the greatest pleasures in life. It is nature’s way of ensuring continuation of the species. Both partners need to be relaxed – it is difficult to enjoy anything in life when you are under stress. All too frequently, poor libido can be related to social circumstances that need to be changed. Medical treatment is only likely to be required or beneficial on occasion.

A couple need time together by themselves. Both partners need to contribute fully to the relationship to be able to reap the benefits. There is a danger that as a relationship matures, the early feelings of adventure and experimentation will give way to repetitiveness and familiarity. When it comes to life in general, and sexual relationship in particular, there is frequently need for personal review. It is all too easy to fall into a rut. Before seeking investigation of your hormone status and perhaps embarking on hormone therapy, check to see whether refining or adjustment of your own lifestyle or perhaps that of your partner is required.

Hormones undoubtedly have an important role in libido with both oestrogen and androgens (Q2.9) being involved. Oestrogen replacement therapy may sometimes provide benefit. Vaginal discomfort or pain due to oestrogen deficiency would clearly be off-putting and this is relatively simple to treat either by HRT or topical oestrogen creams or pessaries (Q28.2). Oestrogen replacement may improve libido by its actions on the higher centres within the brain. Tibolone (Q28.13) has oestrogens, estrogens, progestogen and androgen effects. There is statistical evidence from a study conducted at Guy’s Hospital in London, that it may improve libido.

If oestrogen replacement does not resolve this problem, testosterone tablets (Restandol), injections (Sustenon) or implants may improve the sex drive. These agents are not licensed for use in women but the British National Formulary (a major reference book published for doctors and listing all available medications) confirms the acceptance of the testosterone implants for women. Testosterone implants can also improve general energy-loss problems. Side-effects, such as increased body hair, are uncommon and they generally disappear when treatment is stopped. It seems appropriate to monitor testosterone levels for patients receiving testosterone.

There is a new generation of drugs on the horizon. Viagra appears to benefit male impotence and there are reports that it may improve female libido. If problems with libido persist, the advice of a specialist counsellor should be considered.

Q 28. 1 What happens when I visit my doctor / HRT clinic for the first time?
Q 28. 2 How can local genital symptoms such as vaginal dryness be treated?
Q 28. 3 How will we decide which is the most appropriate HRT preparation for me?
Q 28. 4 What problems might occur when I start HRT?
Q 28. 5 What is the choice of oestrogen-only preparations?
Q 28. 6 How are oestradiol implants introduced?
Q 28. 7 Is it possible for me to be given too much oestrogen?
Q 28. 8 How long will my oestradiol implant last?
Q 28. 9 Why might I require progestogen in addition to oestrogen?
Q 28. 10 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?
Q 28. 11 Could we adjust the timing of the withdrawal bleed associated with sequential (cyclical progestogen) HRT preparations for my social convenience?
Q 28. 12 I have gone through the menopause. Does HRT mean that I must have ‘periods’ again?
Q 28. 13 What is Tibolone (Livial – Organon)?
Q 28. 14 I have had a premature menopause? What forms of HRT are available.
Q 28. 15 Is there an indication for the levonorgestrel intrauterine system (Mirena) in the management of the menopause?
Q 28. 16 Is there a place for progesterone replacement therapy?
Q 28. 17 Is there a place for testosterone replacement therapy?
Q 28. 18 My sex drive (libido) is rather low. Is there anything that might improve it?
Q25.18a What is the place of Viagra (sildenafil citrate) in sexual dysfunction in women?
Q 28. 19 How would the possible advantages and disadvantages of HRT compare for me?
Q 28. 20 What side-effects could I have with HRT?
Q 28. 21 What can be done if I develop irregular bleeding on HRT?
Q 28. 22 If I start HRT, will I gain weight?
Q 28. 23 If I have menopausal symptoms but I cannot take HRT what other options are available for me?
Q 28. 24 How will I be monitored once I start HRT?
Q 28. 25 How long can I take HRT?
Q 28. 26 Do most women continue with HRT?
Q 28. 27 How can doctors encourage their patients to continue with our HRT?
Q 28. 28 Are women who have had higher education more likely to take HRT?
Q 28. 29 Are there any new developments with HRT?
Q 28. 30 What are your conclusions with regard to the risks and benefits of HRT?
Q 28. 31 Could I have some useful Web sites?
Women’s Health – Home Page

Q 28. 19 How would the possible advantages and disadvantages of HRT compare for me?

This is the key question that applies when considering HRT or, for that matter, any other medical or surgical treatment. You need to weigh up the potential advantages and disadvantages (Figure 28.2 and Chapter 27).

Advantages:

• Hormone replacement therapy is indicated to treat symptoms that are attributable to oestrogen deficiency.

• We know that HRT reduces hot flushes and night sweats (Q26. 9).

• HRT may overcome local problems including vaginal discomfort and pain during intercourse (Q28.2).

• Some bladder problems may be reduced (Q26.11).

• HRT may improve menopause-related depression (Q27.1) and mental ability (Q27.2).

• Reduce long-term morbidity (poor health).

• Heart disease (Q27.3)

• Osteoporosis (Q27.9)

• Alzheimer’s disease (Q27.2) may be less common in those who have taken HRT.

• Reduces early mortality (death) that might arise as a rise of postmenopausal oestrogen deficiency (Q27.25).

• There is an overall reduced risk of cancer (Q27.25).

Disadvantages:

• No treatment is without potential side-effects (Q28.20)

• There can be little doubt that the greatest concern for women considering HRT is breast cancer. The additional risk is very low (Q27.15).

• Similarly, the other potential risk of thrombosis is extremely uncommon (Q27.22).

The majority of gynaecologists and physicians believe that for most women the advantages of HRT significantly outweigh the disadvantages. Ultimately it is for you to evaluate the available information and to decide for yourself whether you feel that HRT is the right choice for you. There can be little harm done in putting HRT to the test.

Q 28. 20 What side-effects could I have with HRT?

Unwanted symptoms can occur with oestrogen and also progestogens if combined regimens are required.

When reproductive hormone levels are changing, women report alterations of feelings that they may find difficult to describe. This may happen in pregnancy, after childbirth and when taking hormones (pill or HRT). Many women feel healthier and happier when pregnant but there is a wide variation. Similarly most women feel better on HRT but others may have a negative reaction.

Oestrogens: In one study, sixty-one women received either conjugated equine oestrogens (Premarin) or a placebo (a look-a-like preparation but without the active drug) for six months. The ‘treatment’ was then reversed for a further six months. The women were not told whether they were taking oestrogen or placebo first (a placebo-controlled study Q33.26). Thirteen (21%) reported leg cramps with oestrogens and three (5%) had leg cramps with placebo. Eight (13%) had mastalgia (breast tenderness) with oestrogen but six (10%) had this symptom with the placebo.

A few had eye irritation, fluid retention, nausea, vaginal discharge or limb pains. The authors concluded that the incidence of side-effects was low and they did not cause any major difficulties for the patients. The leg cramps were difficult to explain but they were not associated with thrombosis (Q4.22).

Progestogens: There is little data about the incidence of progestogen induced side-effects. They may be dose related and differ according to the progestogen used. Symptoms attributable to progestogens are similar to those seen in premenstrual syndrome (Q25.1). They may be physical including acne, greasy skin and rashes or psychological with depressed mood, anxiety, aggression and panic attacks.

These side-effects can be minimised or abolished for the majority by ensuring that the smallest safe dose is prescribed. If progestogens are taken for only seven days each month the chance of endometrial hyperplasia (thickening) (Q 28.9) is only 4%. A change of progestogen (or perhaps progesterone gel – Crinone) may be appropriate.

Q 28. 21 What can be done if I develop irregular bleeding on HRT?

A little irregular bleeding can occur during the first few months of taking HRT. It is likely to settle. Your doctor may wish to check that it is the HRT and there is no other cause for the bleeding. At one time D & C (Q24.12) was commonly recommended but these days a tiny tube can be introduced into the cavity of the womb to obtain a small biopsy (sample) of the lining (Q24.9).

Sometimes the bleeding may settle with additional progestogen for one or two months. There are many HRT preparations and a change to another type or strength may be the solution. We also find that a course of antibiotics may help on occasion, presumably by treating bacteria in the uterine cavity.

References:

Unexpected vaginal bleeding and associated gynecologic care in postmenopausal women using hormone replacement therapy: Comparison of cyclic versus continuous combined schedules. (1998 – 3099)

Q 28. 22 If I start HRT – Hormone Replacement Therapy, will I gain weight?

A common anxiety amongst women contemplating HRT is weight gain. There is no evidence, that HRT routinely causes weight gain. A personal computerised search (Medline – Q4.28) of the literature revealed twelve publications that looked at the relationship between HRT and weight. There was no difference in weight change whether HRT was taken or not in eight studies. One study indicated a weight loss with HRT and three found a slight increase with the HRT.

In a study conducted in Jerusalem, women who accepted HRT were compared to a group who declined it. Over the course of one year the average weight gain in both groups was 2kg (4lb) with no statistical difference between them.

The study showed that women were gaining weight whether or not they took HRT. Serial measurements of the waist-to-hip ratio demonstrated a change from the gynaecoid (hour-glass) fat distribution to the android (waist enlargement) in those women not on HRT but this did not occur in the HRT group. In practice, many patients insist that they are gaining weight even when their records show no chang .

This is difficult to explain although two possibilites would be an alteration in shape or possibly a change in self-perception rather than a physical change. There are exceptions to every rule, and on occasion I see women who undoubtedly gain a few pounds specifically when they are taking HRT

References:

Effects of hormone replacement therapy on weight, body composition, fat distribution, and food intake in early postmenopausal women: a prospective study (1995-954)

Q 28. 23 If I have menopausal symptoms but I cannot take HRT what other options are available for me?

At one time many women were advised that they could not take HRT for a variety of reasons that are no longer considered to be contraindications. Diabetes, high blood-pressure, heart disease and obesity were regarded as medical reasons for avoiding HRT but this is no longer the case. Nowadays, there are very few, if any, absolute contra-indications to HRT.

Some women have anxieties about interfering with hormones or cannot find an HRT preparation that suits them. For those with hot flushes, hot flashes, night sweats, clonidine (Dixarit – Boehringer), ethamsylate (Dicynene – Delandale) or progestogens (Q24.17B) such as Provera 10 – 30 mg daily may help.

If the problems relate to vaginal dryness, including discomfort or dyspareunia (pain during intercourse) topical vaginal oestrogen preparations that are poorly absorbed may be considered for vaginal symptoms (Q28.2).

Tamoxifen is frequently prescribed for several years following a diagnosis of breast cancer (Q32.42). This drug has anti-oestrogenic activity, which is probably its mode of action on the breast tumour. Paradoxically, tamoxifen also has some oestrogenic activity on the genital tract so postmenopausal women taking it seem to be less prone to vaginal symptoms

A thirty-one year old lady presented with pelvic discomfort, which was related to fibroids. She came to hysterectomy and her ovaries were removed. The fibroids were benign under the microscope but they had a tendency to recur (an extremely rare situation). When she was given HRT more fibroids appeared (an extremely rare condition called benign metastasising leiomyomata) but they regressed when the HRT was withdrawn. For the last thirteen years she has been taking tamoxifen. The fibroids have not recurred and there have been no problems with menopausal symptoms.

References:

Effect of clonidine on hot flashes in postmenopausal women (1982-962)

Q 28. 24 How will I be monitored once I start HRT?

Initially you are likely to be seen every three or four months. When all are happy with the treatment regimen, less frequent checks will be required. Opinion varies as to the frequency that physical examination should be undertaken.

Some suggest that pelvic examinations should only be performed when taking routine cervical smears, usually at 3 – 5 year intervals. Others recommend pelvic examinations once or twice each year. My own opinion is that those looking after women’s health should consider undertaking a clinical examination at least every 12 – 18 months to exclude the development of obvious disease.

Examination should include a blood pressure reading, breast and pelvic examination. These examinations are not performed because of any increased risk, but purely as it is good clinical practice for doctors looking after to provide appropriate reassurance.

There is usually no indication to check oestrogen levels routinely for patients having oestrogen replacement therapy. Occasionally, a blood hormone test may assist adjustment of hormone replacement therapy if symptoms persist.

A 48-year-old lady with depression seemed to benefit for a while with transdermal patches but then her depression increased again. Her plasma oestradiol test was found to be low on two occasions. An oestradiol implant was introduced and this resulted in symptomatic relief.

Regular testosterone estimations should be considered for women receiving testosterone treatment (Q28.18).

Routine breast screening is recommended in most developed countries (Q32.36). Hormone replacement therapy may be associated with increased glandular tissue making breast x-rays (mammograms) appear denser – it is essential that the radiologist reading the pictures is aware that you are on HRT. Sometimes supplementary tests such as ultrasound may be recommended. We advocate regular mammography for postmenopausal women. If you have been taking HRT for more than ten years, mammography once every year or eighteen months would seem appropriate beyond the age of fifty.

At one time, regular sampling of the endometrium (lining of the uterus) was advocated when HRT involved oestrogen without progestogen. We now know that if you are taking oestrogen replacement together with progestogen supplements your are even less likely to develop endometrial cancer than a woman who have never taken HRT. There is, therefore, no longer a reason to recommend sampling unless there is inappropriate bleeding.

Q 28. 25 For how long can I take HRT?

If HRT is being taken only to correct symptoms (e.g. flushes or headaches), it may be reasonable to stop the HRT after a few months and see whether the symptoms persist. For long-term prophylaxis (prevention) of osteoporosis or heart disease, treatment should continue for several years or perhaps indefinitely. The risk is a slight increase in the incidence of breast cancer (by 1.5% from 7.5% without HRT to 9.0% if HRT is taken for more than 15 years – Q27.15)

If you are happy with your HRT there is no medical reason for you to discontinue it. It is all a matter of benefits and risks. In general, the benefits appear to outweigh the risks.

Q 28. 26 Do most women continue with HRT?

It is now recognised that HRT has been the most important advance in preventative medicine since the introduction of vaccines. Patient compliance (adherence to treatment), however, is variable. Great variation in the degree of patient compliance is reported between different centres. In one study only 40% of those women commencing HRT were taking it reliably after nine months.

There were a number of reasons for this. Some were anxious about the possible risks of cancer or they had heard stories that HRT resulted in weight gain (these stories are disproven (Q28.22). Others were unhappy with side-effects such as headaches, “period” problems or breast discomfort.

Q 28. 27 How can doctors encourage their patients to continue with our HRT?

Primarily by arriving at decisions in a partnership with our patients. Each patient must be involved in decisions about her treatment. Provision of information leaflets that answer key questions allow patients to be kept informed. Recommending the use of continuous combined preparations to avoid withdrawal bleeds after the menopause and regular review encourages women to enjoy the long-term benefits of HRT. Doctors should be willing to change preparations if problems arise.

In 1998, a fifty-seven year old health-visitor was referred to me as her withdrawal bleeds were heavy and she felt poorly for the last week of each course of her sequential HRT. Without HRT she felt “hot and bothered”. It became apparent that neither the patient nor the general practitioner were aware of continuous combined preparations. A continuous combined preparation was prescribed and she has become “a new woman”.

An article in the British Journal of Obstetrics and Gynaecology in 1997 found the information supplied with five HRT preparations was incorrect and misleading. The authors observed that ischaemic (coronary) heart disease, for example, was a contraindication to HRT according to the accompanying information, when the opposite is true (Q27.3). Doctors should encourage the pharmaceutical industry to ensure that their data sheets are modified regularly so that the information they provide to patients is accurate.

References:

Commencement and maintenance compliance of patients on hormone replacement therapy (HRT) following bilateral oophorectomy (2001-3352)

Estrogen replacement therapy in practice: Trends and issues (1995-1909)

A survey of views on hormone replacement therapy (1994-383)

25 mg oestradiol implants – The dosage of first choice for subcutaneous oestrogen replacement therapy? (1992-170)

Enhancing patient compliance with hormone replacement therapy at menopause (1990-1145)

Q 28. 28 Are women who have had higher education more likely to take HRT?

A study in Northern Italy found that women who had received formal education for twelve years or more were three times as likely to take hormone replacement therapy compared to those with seven years formal education or less. Most menopausal women doctors in the United Kingdom have taken HRT and most of them continue to take it for more than five years.

References:

Differences in hormone replacement therapy use by social class, region and psychological symptoms (2001-3340)

Prevalence and characteristics associated with use of hormone replacement therapy in Britain (1997-1661)

Utilisation of hormone replacement therapy by women doctors. see comments

Q 28. 29 Are there any new developments with HRT?

Selective oestrogen receptor modulators (SERMs e.g. Evista – Lilly) are being investigated. These substances selectively produce oestrogenic effects at some sites such as the bones but do not affect other sites such as the breast or endometrium. These new drugs will require a lot more research before we will know enough about their long-term benefits and risks.

References:

Modulation of the oestrogen receptor: A process with distinct susceptible steps. (2000 3142)

The endometrial effects of SERMs (2000-3145)

Skeletal effects of selective oestrogen receptor modulators (SERMs). (2000 3146)

Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. (1998 2321)

Selective oestrogen receptor modulation: An alternative to conventional oestrogen. (1998 2887)

Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. (1997 2318)

Q 28. 30 What are your conclusions with regard to the risks and benefits of HRT?

On current evidence, the benefits outweigh the risks (Q28.19 – Figure 28.2).

There is debate as to how much the support, understanding and care provided may be assisting patients on HRT but this is true for any treatment. Most patients attending HRT clinics report tremendous benefits from treatment and the majority of women have no problems with side-effects. In medicine we look for controlled trials (Q33.26) to provide scientifically validated evidence of efficacy.

To determine the potential benefits and risks of HRT we would have to set up a controlled trial. It is probably impossible now to set up such a controlled study. Those who seek HRT for symptom relief or for reduction in the risks of heart disease or osteoporosis are unlikely to enter a trial where they may not receive the treatment.

For a doctor to withhold essential vitamin supplements and allow the development of conditions such as scurvy would be unthinkable. Failure to provide hormone replacements such as thyroxin for a patient with an underactive thyroid or insulin for a patient with diabetes would be, at the very least, unethical.

The menopause signifies a hormone deficiency state and the effects of withholding hormone replacement can be profound. The medical profession should offer HRT to the majority of postmenopausal women and to pre-menopausal women with oestrogen deficiency symptoms.

Doctors thrive by watching their patients’ health improve with the treatment they prescribe. As a doctor frequently seeing women with menopausal problems, I find prescribing HRT a particularly rewarding exercise.

Many women may have “side-effects” that they attribute to their medication. The fact is that when women are divided into two groups, one receiving the treatment and another receiving a placebo (Q33.26), many on the placebo report side-effects.

We all have different likes and dislikes.

On 15th September 1998 two campaigners against HRT were featured on the national television news. They claimed to represent “thousands” of women disgruntled by the side-effects of HRT. No doubt they would want doctors to provide “evidence-based medicine” but they are happy to make claims unsubstantiated by fact.

The importance of obtaining advice from responsible professional people is discussed in Q4.28. I am not keen on contemporary art but I would not campaign against it. For those women who do not like HRT the answer is very simple – do not take it – but do not frighten other women about medication that may provide tremendous short- and long-term benefits.

Ultimately it is for each woman to decide for herself, from an unbiased summary of the available information, whether she wishes to commence HRT and then to continue with it.

References:

Benefits and risks of estrogen replacement therapy (1995-1908)

Evaluating the benefits and risks of postmenopausal hormone therapy (1991-647)

Q 28. 31 Could I have some useful Web sites?

Evaluation of the quality of Web sites is discussed in Q4.27. You may find that several general women’s health sites may help you (Q4.28). The following are more specialised Web sites on topics found in this chapter: https://2womenshealth.com/

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Q 28. 1 What happens when I visit my doctor / HRT clinic for the first time?

Q 28. 2 How can local genital symptoms such as vaginal dryness be treated?

Q 28. 3 How will we decide which is the most appropriate HRT / Hormone Replacement Therapy preparation for me?

Q 28. 4 What problems might occur when I start HRT?

Q 28. 5 What is the choice of oestrogen-only HRT preparations?

Q 28. 6 How are oestradiol implants introduced?

Q 28. 7 Is it possible for me to be given too much oestrogen?

Q 28. 8 How long will my oestradiol implant last?

Q 28. 09 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?

Q 28. 10 Do all women taking sequential (cyclical progestogen) HRT have withdrawal bleeds?

Q 28. 11 Could we adjust the timing of the withdrawal bleed associated with sequential (cyclical progestogen) HRT preparations for my social convenience?

Q 28. 12 I have gone through the menopause. Does HRT – Hormone Replaement Therapy – mean that I must have ‘periods’ again?

Q 28. 13 What is tibolone (Livial – Organon)?

Q 28. 14 I have had a premature menopause. What forms of HRT are available?

Q 28. 15 Is there an indication for the levonorgestrel intrauterine system (Mirena) in the management of the menopause?

Q 28. 16 Is there a place for progesterone replacement therapy?

Q 28. 17 Is there a place for testosterone replacement therapy?

Q 28. 18 My sex drive (libido) is rather low. Is there anything that might improve it?

Q 28. 19 How would the possible advantages and disadvantages of HRT compare for me?

Q 28. 20 What side-effects could I have with HRT?

Q 28. 21 What can be done if I develop irregular bleeding on HRT?

Q 28. 22 If I start HRT – Hormone Replacement Therapy, will I gain weight?

Q 28. 23 If I have menopausal symptoms but I cannot take HRT what other options are available for me?

Q 28. 24 How will I be monitored once I start HRT?

Q 28. 25 For how long can I take HRT?

Q 28. 26 Do most women continue with HRT?

Q 28. 27 How can doctors encourage their patients to continue with our HRT?

Q 28. 28 Are women who have had higher education more likely to take HRT?

Q 28. 29 Are there any new developments with HRT?

Q 28. 30 What are your conclusions with regard to the risks and benefits of HRT?

Q 28. 31 Could I have some useful Web sites?

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