Information Regarding Progesterone:

The aim of this document is to respond to queries around the use of progesterone in Transwomen.

We are frequently asked about the use of progesterone in transfeminine healthcare from service users and health professionals. We are seeing increasing use of micronized progesterone (body identical progesterone known as Utrogestan) in transfeminine/trans female patients from some private providers. This is off licence use. There are no NHS gender services in the UK that are currently routinely prescribing progesterone.

The WPATH (World Professional Association for Transgender Health) standards of care version 8 states:

“Data to date do not include quality evidence supporting a benefit of progestin therapy for transgender women. However, the literature does suggest a potential harm of some progestins, at least in the setting of multi-year exposure.”

What is Progesterone?

Progesterone belongs to a group of steroid hormones called ‘Progestogens’ or ‘Progestins’ that are produced by the ovaries during the menstrual cycle. Progestogens are secreted by the ovary at higher levels in the first 10 weeks of pregnancy followed by the placenta in later pregnancy.

Almost all breast growth in cis female adolescents occurs before they start to produce progesterone although there is a theoretical argument for Progesterone augmenting breast growth. There is a small amount of anecdotal evidence to back this up.

What is the Benefit of Progesterone in Trans Healthcare?

We don’t know what the benefits are and how many people who use progesterone see these benefits. There are anecdotal reports that for some people it may:

·      Improve breast growth and support feminisation after an individual has had 18 months of Estrogen therapy

·      Improve general sense of well-being

·      Improve sleep

·      Improve libido

It is not known if any of these reported benefits are transient or permanent.

What we know about progesterone in trans affirming care:

·      There is a tiny amount of research, a small number of anecdotal reports and a few opinion pieces

·      Much of the good evidence and data is extrapolated from cis people

·      We need to make pragmatic decisions using this little evidence to weigh up the risks and benefits

What do we know about progesterone from post-menopausal cis women?

Progestogens are used in post-menopausal cis women to protect the endometrium from the estrogen used for hormone replacement therapy (HRT). In postmenopausal cis women, estrogen and progestogen combined HRT is associated with increased risk of breast cancer and increased cardiovascular risk (heart attacks, strokes and blood clots). Meanwhile, estrogen-only HRT is not associated with an increased risk of breast cancer in cis-women, without a uterus. The cardiovascular risk of estrogen-only HRT is also less that of combined HRT, for this group.

However; these studies were undertaken with different forms of synthetic progestogens. We know micronised progesterone is safer than synthetic progestogens. Using a micronised progesterone would be lower risk but would not remove all risk. This is also a different population of post-menopausal cis women.

There is no evidence that progesterone improves libido for post-menopausal cis women.

Side-effects with Progesterone

The progestogen component of HRT for some cis menopausal women causes significant side effects and in some progesterone intolerance. Some progestogens cause masculinising side-effects such as acne and increased body and facial hair. They can cause fluid retention and weight gain. They can be associated with mood changes and lipid changes. These side effects are more common with progestogens and less common with micronised progesterone, but they can still occur and for some individuals be intolerable.

Benefits versus Risks

Some people use progesterone and say it helps with their general sense of well-being. It is hard to quantify this but there may be other medications or management options for ‘well-being’ or mood that are lower risk.

The data around breast growth with Progesterone is poor. We think there is an increased risk of breast cancer with Progesterone but transwomen are at a lower risk of breast cancer than cis women.

There are anecdotal reports of progesterone improving bone health, but again Trans women are at a lower risk of Osteoporosis than cis women. There are also safer management options for bone health than Progesterone.

At the moment there is no evidence of benefit of these agents in terms of feminisation but there are risks. These risks are lower with micronised progesterone. More research is needed and we will continue to watch this space.

To Summarise:

Benefits

·      Possible improved breast growth

·      Possible improvement to ‘well-being’

·      Possible improvement to sleep

·      Anecdotal reporting of improved bone health

·      Possible improved libido

Risks

·      Possible increased risk of breast cancer

·      Possible increase to risk of cardiovascular disease

·      Side effects with Progesterone which can be significant

Potential Side-effects

·      Acne

·      Increased body and facial hair

·      Fluid retention

·      Weight gain

·      Mood changes

·      Lipid changes

On balance, the YGES does not support the routine prescribing of progesterone due to the lack of evidence sufficiently supporting the benefits of progesterone outweighing the risks.

Monitoring

We have no guidelines to direct or manage Progesterone use other than as a trial as detailed above. We would suggest no additional monitoring of progesterone other than the routine reviews which would be required for monitoring Estradiol. A review of the progesterone after six to twelve months would be to think about side effects and if the individual is seeing any of the benefits.

We admit that we as clinicians have seen a small number of patients who have had a trial of Progesterone and found it beneficial. We have also seen patients that have had side effects.

Considering the current evidence and WPATH guidance, YGES feel that the unknown benefits of Progestogens do not currently outweigh the risks.

We are listening to the trans community and talking in expert groups regularly around the use of Progesterone in our hormone team and on a national level. We want more robust evidence and guidelines in this area to support us make these decisions. In the future there may be a place for micronized progesterone but this is not part of our routine care. More research is needed and we will continue to watch this space and advocate for the trans community.