PROGES-TERONE-TIN-TOGEN

... and why doesn't everyone know the difference and why does the difference matter?

Photo by Reproductive Health Supplies Coalition on Unsplash

Hormone specialist Dr Sara Gottfried's appearance on American neuroscientist Dr Andrew Huberman’s Huberman Lab podcast recently was important for a variety of reasons.

First off, it's where I found out that oral contraception reduces testosterone, which among other things, leads to reduced clitoral volume. Hearing Gottfried say that the clitoris can shrink by up to 20 percent from the birth control pill (BCP) almost sparked me to drive off the road. I already knew from experience it was not benign (more on that below), but that clitoris thing has been really hard to process. (Having not measured it, I’ve no baseline.)

Also, to be very clear, I’m not anti-BCP, nor anti-HRT, this is not medical advice, and I’m not trying to scare or trigger or call out anyone who is on the pill or taking progestin in a patch or a pill or through a Mirena coil. There is no reason to panic. I’ve loads of friends and acquaintances who are very happy with it. What I’m trying to do is make sure more people have informed consent and are aware of where the risks – minimal or hard-to-prove causation as they may be – are coming from, when they make decisions about how to deal with their menopause symptoms, and on menopause hormone therapy, aka HT, aka HRT.

Anyway, Dr Gottfried, author of The Hormone Cure, gave a clear and explicit explanation of the difference between progesterone and progestin in reference to the pill, and it’s something I wish all women, and more researchers, doctors and practitioners, were aware of. 

“It’s progestin, so it’s not the normal progesterone that your body makes, that your ovaries make and your adrenals make,” she told Huberman. “It’s a synthetic form of progesterone and it’s the same progestin, same class, that was shown to be dangerous and provocative in the Women’s Health Initiative. So I’m not a fan of progestins.”

Before you say “but Ann Marie the WHI was ALL WRONG” – not everything about the WHI has been discounted. And of course, if you are taking estrogen and have a uterus, you need to prevent the uterine lining from thickening. Progesterone-tin-togen does that. There’s also apparently a difference in how taking progestin or progesterone makes a person feel; it’s been described to me as dramatically as ‘progestin has all the risks and all the side effects, and none of the benefits’. I’ve not felt it; I don’t know. But of course nothing is true for every woman, not all women will do well with either, or have problems tolerating either.

Onwards. With progestin, as Dr Gottfried points out, research has been turning up issues for awhile now.

Take the study Menopause Hormone Therapy and Breast Cancer Risk, published in the June 2022 journal of Obstetrics & Gynecology, which looked at 43,183 cases of breast cancer matched to 431,830 controls.  

Their conclusion? “Although menopausal HT use appears to be associated with an overall increased risk of breast cancer, this risk appears predominantly mediated through formulations containing synthetic progestins. When prescribing menopausal HT, micronized progesterone may be the safer progestogen to be used.”

I learned about that study when Vikram Sinai Talaulikar, a specialist in reproductive medicine and an honorary professor in women’s health at University College London (also coming up on the podcast), tweeted about it with this comment: "Evidence keeps accumulating that estrogen on its own in HRT does not increase risk of breast cancer and the type of progestogen matters."

It was like someone opened a window, because when you are sitting in Abu Dhabi wondering why more people aren’t talking about something, and then you see more and eminently qualified people talking about it, it’s literally emotionally refreshing to not feel like a crazy obsessed loon.

However, demonstrating what tends to happen when estrogen is involved in a conversation – like me when I get excited about something, it takes over – in the US leading ob-gyn Dr Sharon Malone shared Talaulikar’s tweet with this: “I’m might to retweet this every day until someone pays attention. The number one reason why symptomatic women avoid estrogen after menopause is fear of breast cancer. This study upends that. Share this study with doctors who don’t follow #menopause.”

Yes, I get it, awesome – estrogen doesn’t seem like a problem. There’s a whole book about it, 2018’s Estrogen Matters by American medical oncologist Dr Avrum Bluming and social psychologist Carol Tavris. (Which I’ve not yet completed, mea culpa).

But that doesn’t mean there isn’t a problem. When the conversation about HRT is, as most HRT conversations are, focused on estrogen, it not only misses a big part of the story, but it allows this progestin-progesterone distinction to be continually left out of the equation. 

In a new study released in Plos Medicine this month, researchers looked at a group of 9,498 women under 50 who were diagnosed with invasive breast cancer between 1996 and 2017, and compared them to 18,171 closely matched controls, who took progestogen preparations of the birth control pill. They found that 44 percent of the women with breast cancer and 39 percent of those without had obtained a hormonal contraceptive prescription within five years.

They then conducted a meta-analysis of 12 other observational studies on progestogen-only pills – to be clear, they are referring to synthetic forms here – conducted between 1995 and 2022. Their overall findings found a similar increase in risk to combined pills. In their words: “15-year absolute excess risk of breast cancer associated with use of oral contraceptives ranges from 8 per 100,000 users (an increase in incidence from 0.084% to 0.093%) for use from age 16 to 20 to about 265 per 100,000 users (from 2.0% to 2.2%) for use from age 35 to 39”.

They also acknowledge that their findings look only at this issue in the short-term; “they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk”. What happens to those numbers, you have to wonder, when you look into the 40s, 50s and 60s?

And then there are the progestin findings from the large French E3 cohort study of cancer risks in women; included in this study in Breast Cancer Research and Treatment back in 2008 on the “unequal risks for breast cancer” associated with different forms of HRT. I’ve only seen the abstract, which concluded that the progestogen was important consideration to make in breast cancer risk, and that progesterone, or another synthetic form called dygesterone, “could be preferable”.

There’s more, but all of that just talks about breast cancer, none of the other possible implications – and that is too much to consider here, now.

Early on in Hotflash inc, I started to notice that there was a weird vibe around progesterone. And I have to say, starting out, I didn’t really know much about the “Progesterone-tin-togen” distinction either. (I didn’t know a lot of stuff I thought I knew, so I’m super curious what will be in my brain in 2026).

Part of the weird vibe I noticed was that mainstream doctors I interviewed or watched on social media or read quoted in mainstream media didn’t seem to care about any of it much at all other than as a uterus-protecting necessity, and many of them didn’t seem to really notice or rate the difference, and it continues to this day.

Contrast that to the naturopathic and integrative world, and those rare mainstream doctors who manage to practice holistic medicine, and who do understand the difference and believe progesterone is an essential piece of our good health.

University of British Columbia endocrinology professor and researcher Dr Jerilynn Prior has spent her life studying women’s menstrual cycles along with the peri/menopause transition and is a leader in this field. Her research is vital, but also Sisyphus-like. Her findings point to the value of progesterone first, and sometimes progesterone only, in treatment of perimenopause symptoms. Major bodies, including the most recent guidance from the North American Menopause Society, back the use of oral micronized progesterone for hot flashes, mood issues and sleep. But also tend to focus on estrogen.

The bottom line, as Canadian naturopathic doctor and author of hormone repair manual Lara Briden wrote recently when she updated her excellent blog post Progesterone Is Just as Important as Estrogen for Women’s Health, “Women have two main ovarian hormones, not one, and physiologically, estrogen and progesterone work as a team”. I recommend you read the entire post; she lays out why progesterone is important, how it works, and why it is overlooked and misunderstood – confusion with progestin reigns here – better than I ever could.

But somehow, this is usually a prickly thing to discuss.

To me, there are three big questions:

• Why aren’t more people looking at available data and comparing progestin to progesterone in relation to almost every risk that is linked to HRT in general?

• How can any study on HRT that doesn’t appear to separate out what form the women involved were taking, possibly produce reliable results, or lead to any reliable conclusions?

• Why is there so much resistance to discussing this and who might the fog of confusion and lack of clarity be benefiting, and who does it harm?

But this isn’t just about commercial interests, and money and power. (And the push-pull between pharmaceutical companies, which at great expense for potential profit develop delivery systems and formulations of synthetic and bioidentical hormones, secure regulatory approval and sell them en masse, and the compounding industry, which formulates bioidentical hormones in individual batches in labs that are overseen by the appropriate regulatory body. No judgement on either; we need both.)

To the left, to feminists, the BCP is an incendiary no-go – and that is clearly a big part of the chilling impact on discussion. I recently interviewed the British writer Holly Grigg-Spall, author of the 2013 book Sweetening the Pill, for the Hotflash inc podcast (coming soon). The book was the basis for the 2022 documentary The Business of Birth Control, which is compelling (I watched it this week) and was welcomed in some circles, but predictably controversial and not well-received in the main. (Holly herself has paid dearly in her writing career for tackling the subject; she also told me she still gets people saying this isn’t the right time to ask questions).

Things have gotten even more difficult in the US since Roe v Wade was overturned; where in many places the BCP seems like the last bastion of reproductive freedom. It’s one of those many sacrosanct topics You Just Don’t Ask Questions About.

I’m a journalist writing about the peri/menopause space and a woman who took a progestin-only pill for 12 years, starting from the age of 16 to “regulate my period”. (Of course, we now know it doesn’t really do that, because it suppresses ovulation and those are not real periods, no matter how real and regular they seem.) I remember early on, confidently telling other people that because my pill was “only progesterone”, that meant it was safer. I still hear women on social media – and in real life – saying and believing the same thing about their progestin.

This is about taking something and not knowing the entirety of its potential impact on health and vitality – despite having decades of time to study it and get the word out about it – and seeing that all this time later, the majority of people still don’t seem to have that information.

Personally, I’ll never know if the decades of emotional highs and lows and gut dysfunction (waved off as Irritable Bowel Syndrome, with no treatment offered or tests conducted) that started after I went off my pill are connected to the gut dysbiosis I ended up with in the autumn of my perimenopause, and the constellation of symptoms and issues that came home to roost in my body and I am just now working out. I just can’t help being angry that after all this time, we are not further on in our discussion. (And about the possible shrunken clitoris, of course; I’m incensed about that.)

There’s no closure, no way to wrap this up neatly here. While everyone continues to argue and obsess about estrogen, progesterone-tin-togen gets ignored, and that is a shame.

Because information is power. Informed consent is our right. And the more you know, the better you can take care of yourself throughout this transition – and beyond.

Editor’s note

Gosh I meant to give you a whole bunch of news this weekend in addition to this, but I got started on Progesterone-tin-togen and here we are. I wanted free subscribers to have this, because I think it’s really important. Back to the regular rundown next week. Please tell me what you think, what you’d add, what I got wrong – I’m truly curious and interested. I could have done so much more. But this is it for now. Hope you are having a lovely weekend.

AMx