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 (20). 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%.

Figure 28.4

The amount of progestogen required varies between individuals. As with any medication one tries to prescribe the lowest amount required to achieve the objective. Some women have side effects from the progestogen such as premenstrual syndrome type problems. For some patients it may be necessary to increase the progestogen to prevent light bleeding at inappropriate times. If problems arise, a different progestogen may be considered.

There is one preparation, Tridestra (Orion) which has the progestogen for 14 days but on a three-monthly basis. This has the benefit of three-monthly rather than monthly withdrawal bleeds for women thought to be close to the menopause. Several companies provide packages of oral oestrogen with sequential progestogens (Figure 28.1C; Table 28.5).

  Table 28. 5 sequential HRT preparations (cyclical progestogen tablets).

PREPARATION

OESTROGEN/PROGESTOGEN

 mg

COMPANY

TABLETS

Nuvelle

Oestradiol / Levonorgestrel

2 / 75mcg

Schering

Climagest 1 mg

Oestradiol / Norethisterone

1 / 1

Novartis

Climagest 2 mg

2 / 1

Novartis

Cyclo-Progynova

Oestradiol / Levonorgestrel

1 / 0.25

Asta

Cyclo-Progynova

Oestradiol / Levonorgestrel

2 / 0.5

Asta

Elleste Duet 1mg

Oestradiol / Norethisterone

1/1

Searle

Elleste Duet 2mg

Oestradiol / Norethisterone

2/1

Searle

Femoston 1/10

Oestradiol / Dydrogesterone

1 / 10

Solvay

Femoston 2/10

Oestradiol / Dydrogesterone

12/ 10

Solvay

Prempak-C 0.625

Conjugated oestrogens/Norgestrel

0.625 / 0.15

Wyeth

Prempak-C 1.25

Conjugated oestrogens/Norgestrel

1.25  / 0.15

Wyeth

Premique Cycle

Conjugated oestrogens/

 Medroxyprogesterone acetate

0.625 / 10

Wyeth

PREPARATION

OESTROGEN/PROGESTOGEN

 mg

COMPANY

TRANSDERMAL PATCH + TABLETS

Estrapak

Oestradiol / Norethisterone

50 mcg/ 24hr / 1

Ciba

Evorel-Pak

Oestradiol / Norethisterone

50 mcg/ 24hr / 1

Janssen-Cilag

Femapak 40

Oestradiol / Dydrogesterone

40 mcg/ 24hr / 10

Solvay

Femapak 80

Oestradiol / Dydrogesterone

80 mcg/ 24hr / 10

Solvay

 

Most have a continuous daily amount of oestrogen but Trise quens and Trise quens Forte (Novo Nordisk) have varying amounts of oestrogen designed to imitate the natural cycle.

For those who prefer to avoid tablets there are currently three transdermal patches with sequential progestogen applied during the second half of the cycle (Fig. 28.1 C; Table?28.6).

Table 28. 6 sequential HRT patches.

PREPARATION

OESTROGEN/

PROGESTOGEN

 mg

COMPANY

Estracombi?

Oestradiol / Norethisterone

50 mcg + 250mcg/ 24h

Ciba

Evorel Se qui?

Oestradiol / Norethisterone

50 mcg + 170mcg/24 h

Janssen-Cilag

FemSeven Se qui

Oestradiol / Levonorgestrel

50 mcg

10mcg /24 h

Merck

Nuvelle TS?

Oestradiol / Levonorgestrel

80 / 50 + 20 mcg /24 h

Schering

The Mirena intrauterine system (Mirena), an intrauterine system that slowly releases the progestogen levonorgestrel, offers progestogen protection of the endometrium on a continuous rather than a sequential basis. This can be introduced before the menopause when it has the benefit of providing contraception and usually reducing menstrual flow. It may also be considered after the menopause for women requiring HRT who cannot tolerate progestogen administered by other routes.

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