PROGESTOGENS IN HRT

The menopause is technically your last natural period. It occurs due to reducing numbers and quality of eggs in your ovaries. During your menstrual cycle, an egg develops in a follicle, which produces oestrogen. After ovulation (egg release), the remaining part of the follicle also produces progesterone. The progesterone changes your uterine lining that has already been thickened by oestrogen so that a fertilised egg can implant and develop. As your eggs reduce in number and quality in the run-up to the menopause, they fail to respond to stimulation, and you produce less oestrogen. This results in menopausal symptoms.

This article was included in issue 99 (winter 2023-24) of The Menopause Exchange newsletter.

Oestrogen and progesterone
Doctors have known since the 1970s that they can’t simply replace oestrogen for most menopausal women. Unless you have no uterine lining, you’ll need progesterone or a synthetic progestogen as well. This ensures there’s no progressive oestrogen-driven stimulation of your uterine lining, which could lead to hyperplasia (a precancerous state) or even endometrial (uterine) cancer.

Women who have had an endometrial ablation procedure will have lighter or even no periods, but doctors can’t assume they have no uterine lining, so these women still need progestogen with their prescribed oestrogen. Similarly, women who have had a hysterectomy but have been diagnosed with endometriosis have potential uterine lining that needs to be protected. Oestrogen is only used on its own after a hysterectomy without these complications.

Progestogens in HRT
Progestogens are used in two different ways in HRT. If you’re still having some periods, sequential regimes are used. Using additional progestogen for 12 to 14 days mimics your natural menstrual cycle. When the progestogen is stopped, the withdrawal triggers your endometrial lining to break down and be shed.

Once a year has passed since your last natural period, you’re regarded as postmenopausal. This lack of significant ovarian activity leads to relative stability and an absence of bleeding. Your own hormone profile is of low oestrogen and no progesterone (which is naturally only produced after ovulation). When replacing oestrogen in this way, doctors use lower doses of progestogen or progesterone continuously. This blocks stimulation from the oestrogen that’s been prescribed to relieve your symptoms. This type of HRT is period-free but not necessarily bleed-free, as you may bleed early on while your uterine lining stabilises.

Vaginal oestrogen products are highly effective locally but in standard doses these don’t raise blood levels and therefore don’t stimulate your uterus. These can be used without additional progestogen.

Progesterone or progestogen?
Both progesterone and synthetic progestogens act on many body tissues. Doctors choose which one to use after considering what they want it to do, while avoiding potential cancerous changes. The synthetic progestogens in the ready-made sequential combinations can be more effective in controlling bleeding patterns and may be helpful for perimenopausal women with erratic bleeding.

Three-month HRT cycles were used in the past, with a higher dose of progestogen for two weeks at the end of the cycle. Doctors no longer use these as first-choice options as these don’t protect the uterine lining as effectively. There’s also often breakthrough bleeding in the 10 weeks of the oestrogen-only part, and then the side effects of a bigger dose of progestogen and heavier bleeding aren’t welcome.

Specialists may use progestogens that are used for contraception if extreme perimenopausal hormone fluctuations are causing problems with mood, breast tenderness or other physical symptoms. These progestogens act on the brain to block egg release and therefore the hormone swings of the second half of the cycle. Specialists will be careful to ensure that the dose is high enough to protect the uterine lining. Not all doctors are happy to prescribe in this way as it’s technically outside the medicine licence. Most will be comfortable to prescribe a contraceptive progestogen alongside conventional HRT.

If you’re using progestogen-only pills or an implant for contraception and you’re not bleeding but find that menopause is a problem, doctors would advise adding a continuous HRT rather than a sequential combination, even if you don’t know what your periods would be like without it.

A Mirena coil will reduce bleeding (often to zero), protect your uterine lining, and provide a high level of contraception by delivering levonorgestrel directly into your uterus. Very low levels of levonorgestrel will be absorbed into your circulation but these are much less than with any other method and are generally well tolerated. Oestrogen can be added to relieve your symptoms without the need for generalised progesterone, and this has made the strategy very popular.

Progestogen suitability
Some women find progestogen causes mood changes similar to PMS. Different types of progestogen have different effects: this is very individual and difficult to predict. Thinking about how you have got on with hormonal medicines in the past may provide a clue.

Breast cancers are tested for oestrogen and progestogen receptors to guide treatment choices. Both hormones influence the growth of existing cancers. Progestogens differ slightly in their effect. Using hormone treatment after breast cancer is rarely offered.

Progestogens may differ very slightly in their effect on blood clotting but for most women, other considerations will determine which progestogen is used and how they take it.

About the author
Dr Sarah Gray is a GP specialising in women’s health. She has retired after 36 years in the NHS and runs St Erme Medical in Cornwall, which offers private practice.

Created Winter 2023-24
Copyright © The Menopause Exchange 2024

Tags: HRT, menopause, Mirena Coil, oestrogen, ovaries, postmenopausal, progesterone, progestogen