This is a preliminary version of the talk I gave on Feb 17, with Dr. Kristen Vierregger at the USC School of Medicine. Her part of the presentation is separate, in a powerpoint file, and I will prepare it into a web format as soon as we have a final copy. Mine was just a text file, though, so it’s easy to post here. If I were to give a title to my part of the talk, it would be “Patients Are Demanding Better Outcomes In Their Feminization.” Note that since this is a transcript, there are no references or footnotes. For deeper exploration of these topics, see the other articles on this site.

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My partner is a trans woman. I met her about 5 years ago. When we were dating, and getting to know each other’s bodies, I noticed her belly. It was firm and somewhat distended. And silently I felt my heart drop. “How long were you on Spironolactone?” I asked her. “About ten years,” she answered. I had recognized what is sometimes called, “Spiro Belly” — visceral fat, not adipose fat, in the abdomen, which is associated with long term use of Spironolactone at doses over 100mg per day. Ironically, she told me that she had done most of her transition using compressed pellet implant as her estradiol source — which meant that it was unlikely she needed any kind of antiandrogen at all most of that time, because the estradiol itself was entirely capable of suppressing her testosterone level. She didn’t know that, of course. She’d been told that the Spiro was a necessary component of her HRT. I couldn’t bear to tell her that her chance of a classic hourglass figure was gone, that the visceral fat was more or less permanent.

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I’ve seen this a lot. I run a Facebook group dedicated to MTF hormone therapy discussion. It has over 10000 members now and is the largest such group anywhere. I started it a few years ago. One of the first things I learned about trans groups is that they want to post selfies of themselves — and breast shots. Then, those with the most attractive development get this reaction: “I wanna be on whatever SHE’s on.” That’s NOT a way to choose a hormone regimen! I had to fix that. So all personal photos were banned. Eventually nearly everything was banned except links to scholarly articles and medical studies. Then the group morphed into something none of us expected — a forum for new HRT options. Many patients were informed of the dangers of Spiro, of antiandrogens, of advantages of estradiol-only transition… and they began audaciously demanding different treatment from their doctors… and then, some of those doctors became curious what was going on and investigated the group. Two of them found enough of interest there to begin rethinking the Orthodox Protocol and trying a different approach to their patients. One was Dr. Will Powers, who published a protocol showing when estradiol injections were required to avoid E1/E3 antagonistic blocks to feminization. The second is Dr. Kristen Vierregger, who is here with me today, who has unlocked more of the secrets of HRT-based feminization, and why it is so difficult for some of us. Their leadership may make what happened to my partner a thing of the past.

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In the group, we put 3 basic ideas in front of the patients in the hope they will talk to their doctor. Idea one. Estradiol suppresses testosterone. When administered properly, it can suppress it to female or castrate levels. Safely. Idea 2 is: antiandrogens can frequently cause harm to trans patients, especially because of emotional and cognitive effects, and transgender people are especially vulnerable to depression and anxiety. They can become suicidal or at least miserable from transition alone, and don’t need drugs to make it worse. And idea number 3: Progesterone, in the human-identical form, when taken properly, can be a valuable adjunct to MTF HRT in a number of important ways.

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Sadly, all three of these ideas are STILL controversial today.

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Even before I met my partner, who was a Spironolactone patient, I’d watched my best friend end up in the hospital on the 3rd day after her first dose of Spiro, with a full body rash and some kind of heart problem. I knew enough about Spiro at that time to ask her, “Why? Why are you taking this?” She answered “Because my doctor is an expert and she told me I needed it.”

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Spiro is a steroid which, in very high doses, blocks androgen receptors and by affecting the Mineralocorticoid system, indirectly reduces production of testosterone. Its use in MTF trans women is entirely off label. It’s notorious in our online community as the cause of fatigue, cognitive problems (“Brain fog”), muscle cramps, anxiety, depression, short term memory problems, and accumulation of hard belly fat. In a recent survey of 210 people in our online group taking Spiro, 90% reported one or more of these side effects. Our research implies that the visceral fat is due to a slowly increasing rise in cortisol levels, which affects those who are taking more than 100mg a day for over 12 months. A lot of patients complain about poor breast development also, and a small British study seems to confirm that Spiro patients lag behind others in development. So here we have a drug which seems to cause poor breast development, a permanent tummy bulge, and makes you feel mentally crippled or distressed. Honestly, it’s a testament to the determination of trans women to achieve their goals, that they even stick to such a regimen. And again, many are afraid to complain, or are resigned to it as the suffering that goes with part of their transition.

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The kicker is… an HRT can be accomplished entirely without antiandrogens. Estradiol completely shuts down testosterone production in the testicles, if it is present at levels about ten times normal male levels, or about twice average female levels. This has been known for at least 85 years. Prostate cancer treatment used to consist entirely of estrogenic drugs.

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The idea of an estradiol-only transition seemed obvious to me, since I’d never taken any kind of antiandrogen myself, relying on Estradiol Valerate injections, sometimes with progesterone, to suppress testosterone. I’d been interviewing trans women about their HRT since the 80’s, and had seen this over and over. But group members today usually begin on this “Orthodox Protocol” of estradiol tablets and Spiro. They tend to be afraid to complain to their doctors about poor feminization – for fear of losing their HRT entirely. So when they arrive in the group, they are bursting with worry, that they are missing out on better options, and they have a profound dissatisfaction. Those who change to injections report — nearly 100% of them — that they experienced an enormous leap forward in their progress. They become spokeswomen for injections to others. But many of them run into opposition from their doctors.

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I hear these kinds of objections: “My doctor says that long term estrogen levels produced by injections are too high, so he is keeping me on pills.” This is the big one, mostly arising from the proven risks of taking Premarin, a concoction of horse estrogens marketed by Wyeth. But today studies show that transdermal and injected estradiol has little or no cardiovascular, cancer, or thrombosis risk. I traced some old Endocrine Society source studies which raised the spectre of “estradiol overdose” despite knowledge that pregnancy levels are up to 100 times higher. When taken by injection, levels are easy to adjust by varying the dose, using the correct syringe, and low estrogen levels arrived at by injection tend to produce more feminization, faster, than low estrogen levels arrived at by most other methods (due to negative effects of pill-derived estradiol antagonists). A key Swedish study followed about 1000 patients never before treated with antianrogens, whose testosterone was kept at castrate levels for decades by estradiol injection, with 100% success, and no serious side effects.

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Another objection patients report: “My doctor worries that I will hit my sciatic nerve when I inject myself.” In all my 35 years of peer support I’ve NEVER heard of a trans woman hurting herself this way. But if that’s a sticking point, the alternative is subcutaneous injection which works as well as IM. That’s the method I’ve used for years. In our group, about 12% now of those who inject use subcutaneous injection.

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Then there is: “My doctor is concerned with thrombosis with injections.” Studies show this is not a significant risk, even with high estradiol levels, as long as the estradiol is transdermal or by injection. And then: ““My doctor says injections cause your estrogen levels to spike dangerously high.” …but this doesn’t happen for a proper gluteus or subcutaneous injection. It might be true for thigh injection, though the levels are again, not actually dangerous, just wasteful… Then we hear this: “Injections cause major mood swings.” These are usually due to injecting on a 14 day schedule, or injecting improperly in some other way such as by thigh. We’ve had so many people say “I tried injections but had terrible mood swings.” and the first thing I ask them is “Were you injecting into your thigh? Or spacing your injections more than 7 days apart?” Usually the answer is yes. When they change their method, the mood swings disappear.

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There’s a lot more I could say about antiandrogens. Some are not as mentally crippling as Spiro, though all of them can trigger depression. But the key fact is that they are an unnecessary drug, a drug which has higher risk than parenteral estradiol. Why prescribe a drug that causes your patients to experience anxiety, depression, or be at risk for addictive behavior or self harm, when a safer alternative exists? Isn’t it against a principle of medicine to give unnecessary drugs?

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One of those antiandrogen drugs is Finasteride, also known as Propecia. It’s a hair drug for men. But trans women are asking for it, and getting it. Finasteride works by suppressing 5aR, the enzyme which converts testosterone into the more powerful form DHT, which causes male pattern baldness. Now, all older trans women are freaked out about losing their hair. The magic word “regrowth” is enough to get the attention of most older trans women. But, Finasteride causes a variety of depressive symptoms, apparently due to a complex process of unbalancing neurosteroids in the brain — a process which doesn’t always reverse when the drug is stopped. The drug is blamed for a number of suicides in men and there is a giant lawsuit in progress. Frankly, many of us in the group have a gruesome game we play… when we learn of a trans woman suicide, we try to learn whether she was taking Spiro and Finasteride in combination. Many times it has been true. That doesn’t prove anything of course… but in the case of Finasteride, group knowledge has a solution. It turns out that there is an even more powerful suppressant of 5aR than Finasteride… called Progesterone. Men can’t take it… but we’re not men, are we? Informal testing has shown that progesterone, when taken in the right way, is as effective as Finasteride or more so. Hair regrowth can be substantial. And it assists with breast development, and softens skin, may further improve the safety of parenteral estradiol, and assists with suppression of testosterone and testicular atrophy.

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But by progesterone I do NOT mean the various progestins marketed as patent medicines. None of them have the activity of actual human-identical progesterone, and the confusion between the two is one of the most frustrating obstacles to good HRT a trans woman can run into today. As doctors, and medical students, you know that every time a woman gets pregnant, her risk of breast cancer drops about 10%… and it is thought that it is the exposure to the breast maturing progesterone that is the benefactor. Real progesterone, when used with estradiol, actually lowers cancer risk… and cardiovascular risks… while progestins like Medroxyprogesterone do the opposite. My therapist once told me she thinks about 20% of trans women taking Medroxyprogesterone end up with severe depressive episodes, and about 5% of them have psychotic breaks of some kind.

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The difficulty of course is that human-identical progesterone is tricky to take effectively… it can be applied directly to the scalp, but the best method is to inject it. However with its very short half life, you would need to inject it 3 times a week to keep a reasonable level. Doctors usually assume that no patient would be willing to do that… but I do, and I know many others also. However, progesterone is also available as an oral capsule — which has low bioavailability due to mostly being destroyed by stomach acid… but when this capsule is used as a suppository, it is well absorbed, as well absorbed as an injection.

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There is so much more we have learned, or at least… think we have learned. Like how to use progesterone to achieve a high speed testicular atrophy. Or the optimum blend ratios for estradiol and progesterone. Or how to use injection intervals to adjust for uptake at different injection sites. Or using Rutin to reduce any remaining risks of thrombosis. Or using Pregnenolone to prevent Morning Blues from changing hormone levels. And much more. I could stand up here and talk all morning. But before I go, I know I probably have said something that made you think “Can she prove that with real research?” and the answer is usually yes. If you visit my web site, you’ll find a lot of articles and I’ve provided detailed references there. That web site is moderntranshormones.com. I suppose I will post the text of this talk there too once I get home. So I thank you for listening, and I’ll be glad to take any questions you might have when we get to question time.

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