What’s the history of using progesterone in gender affirming care? When and how do we use it in transgender and gender diverse health?
Pearls:
- we use bioidentical micronized!
- most research is in menopausal cis women
- ovaries make both estrogen and progesterone, so why don’t we include it?
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Video Transcript
since we started talking about progesterone
let’s keep going
first let’s talk about why progesterone is like
less used in gender affirming care and the history of that
and then also
potentially the reasons why it’s somewhat
um contentious
so the reason progesterone is not in the guidelines in
wasn’t used historically in gender affirming care
is the Women’s Health Initiative
which was a study that was done about 30 years ago in postmenopausal
CIS women looking at hormone replacement um
for the prevention of cardiovascular diseases
the age and the study arm of that trial that use progesterone um
did have a statistically significant increase in VTE because of that uh
the that portion of the study was actually stopped early
now if you look at the issues with progesterone in that study
you will see that although it is statistically significant
it was a very small increase in incidences
and that overall mortality was not increased furthermore
the progesterone used in that study
is not the same progesterone we currently use in gender affirming care
which is bioidentical
so we typically use micronized
progesterone which um
all the literature to date
shows absolutely no increased risk in VTE with that form of progesterone
so because that study showed progesterone to be
quote unquote
less safe um
it was avoided
and both hormone replacement for postmenopausal CIS women
and in hormone therapy for transgender
diverse folks
and so because it was avoided
it’s not included in the publications
research and guidelines um
because it was used less typically
now here we are
30 years later
and we have a safer form of progesterone available to us and um
we have to think about
how well does research and data
and post menopausal CIS women translate into trans & gender diverse patients
and it really depends on the individual trans and gender diverse patient
what age are they
what are their pre existing health conditions um
and to really understand how to try to interpret that data
onto their individual risk
because of that history in those guidelines
we don’t have a lot of research or information about the use of progesterone
and trans and gender diverse folks
and that paucity of data has caused a lot of the major recommending bodies
and guideline writing organizations to say
we can’t make a recommendation for against it
cause we don’t have enough information um
and then if you look at the newest WPATH SOC8
they bring up a concern around breast cancer
but if you look at the reference article that they use for that
it is not actually like a meta analysis or a trial
or any kind of data that actually shows an increased incidence in breast cancer
from the use of micronized progesterone
it’s an opinion piece from a clinician who says
theoretically
the risk of breast cancers
might be higher with the use of micronized progesterone so I’m
on the side of this like
debate in gender affirming care that I’m pretty pro progesterone one
I think every individual patient should be treated as an individual like
we should be looking at their goals and discussing their goals with them and um
offering them counseling
whether or not progesterone would help reach those goals or help fit those goals
and then the individual risk and benefits for them
but in general
when I think about what I’m doing
as a prescribing clinician for trans and gender diverse patients
I’m often times trying to replicate the function of an ovary
and ovaries do make estrogen and progesterone
so physiologically
it seems a little odd to me to only do half the job um
especially when I know
I have a safer form of progesterone
that the original risk and concerns around progesterone are no longer valid
um furthermore
when I think about the physiologic function of progesterone and estrogen
at target tissues
I do remember from my medical training right
that they often actually act in opposition of each other
to create ideal tissue environments through a remodeling process
right like we see this in the level of the bone
where we have osteoclasts
osteoblasts responding to estrogen and progesterone
to remodel the bone and optimize bone health and strength
it’s the same thing in the endothelial lining of the blood vessels right
we know that estrogen and progesterone work in opposition
to keep that tissue optimally remodeled and flexible
and which helps reduce risk of cardiovascular disease
and we do see in the literature that CIS women with like
lower naturally occurring levels of progesterone
actually develop cardiovascular disease disease sooner than their peers with
more average or higher levels of progesterone
and so I have to wonder that if by doing an estrogen only
gender affirming care
if by not considering offering and including progesterone
I’m increasing the risk of osteoporosis and cardiovascular disease
for my trans and gender diverse patients as they age
this is all theory
we don’t have any evidence or literature around this
um in addition to like
that oppositional effect at target tissues
we also know that progesterone often works hand in hand with estrogen to
to bring about secondary
secondary sexual characteristics right
we know that progesterone is essential in the development of a breast tissue
to take it from the adolescent phase to the adult or mature phase right
to get from Tanner 3 to Tanner 5
it is essential for the creation of mature tissue
and a lot of patients will say they do feel like they have you know um
better breast development when we add progesterone
that’s clinical experience
that’s patient experience
it is not evidence based
if you’ve ever tried to measure a
a three dimensional
squishy object like boobs
it’s really hard
if you look at the research and literature
trying to do studies on breast and breast development and breast size
they have all these different strategies for measuring them
and none of them are very effective
um that being said
in a field where we have such a lack of evidence based information
I think clinician opinion and experience
and patient opinion and experience becomes that much more important
that doesn’t mean I don’t want us to continue to
advocate and strive for more evidence based information
of course I do
of course I want more research funded to help support my community and
and our educational knowledge but
evidence based medicine has multiple different levels of grading of information
and expert opinion is one of those levels
it is not considered the highest
is not considered you know
quote unquote the best
and we also know evidence based medicine is sometimes just wrong right
like historically
we looked a whole bunch of cholesterol levels
and so this is like the quote unquote healthy cholesterol level
and it was actually too high because we just like normed um
in average values we looked at in a specific population
and we often do a very
very bad job of diversifying our populations and being inclusive
um and so evidence based medicine
yes very important
I tend to call my work in gender affirming care evidence informed
to give that slight differentiation between
the fact that evidence based medicine is very lacking in my field
and I do my very best to stay um
on top of engaged and informed about the research and literature
but that ultimately what we’re doing is a really big blend
of that evidence and literature
my clinical experience
and the GREATER BODY of trans wisdom that exists within our community
Other QueerDoc articles about progesterone:
- Progesterone – The Big Debate
- Progesterone- Why’s it Missing?
- Gettin’ Nerdy on Gettin’ Curvy: Estradiol, Progesterone, and SERMs

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