On the Science of Changing Sex

Love’s Labour’s Lost

Posted in Transsexual Field Studies by Kay Brown on September 29, 2010

About fifteen years ago, in my mid-30s, my physician switched me from Premarin to the so called, “bio-identical hormones” estradiol and micronized progesterone. She told me that she had seen better results with other clients, and thought I would as well. I can personally attest, she wasn’t kidding! Even after twenty years of taking Premarin (conjugated estrogens from pregnant mare’s urine) and/or Estinyl (17α-ethynylestradiol) with intramuscular injections of medroxyprogesterone, I was still fairly flat-chested. The new ‘meds’ fixed that! While welcome, the real surprise is how much the new protocol improved my libido. As I had begun HRT in my teens, I hadn’t noticed any drop off for the first years, perhaps because I couldn’t afford surgery until I was 23? But even then, the drop off in libido had been slow, only showing a severe drop during and subsequent to a life threatening illness I suffered around my late 20’s. It had taken years to recover my health.

After I shared my observations regarding the new meds and its effect on my romantic life, my doc then told me that she had noticed a bimodal response to the new protocol. While all of her clients showed better breast development and feminizing fat redistribution, her “young transitioners” had nearly universally experienced noticeably increased libido compared to her previous protocol of using Premarin or Prempro for post-ops. However, the effect was not as strong with her “late transitioners”. She hadn’t told me to expect the possible increase in libido because she didn’t want to induce a possible placebo effect. As a primary care physician, she was more concerned with providing the best care for her clients, then for publishing, so I don’t know of any papers where this bimodal response has been noted in the literature.

There is however, a very good paper on the effect of MedroxyProgesterone Acetate in experiments with female macaques. Medroxyprogesterone Acetate (MPA) is the synthetic progestin that is in Prempro, Provera, and Depo-Provera. It’s also in a number of contraceptive pills. Female macaques, like human females, are physically capable of having sex at any time in the estrus cycle, making them ideal candidates for experiments on the effect of hormones on libido. The macaques had had their ovaries removed. This caused them to lose interest in sex. When given estradiol their libido returned. Given a combination of estradiol and MPA their libido was killed. As a side effect, the MPA also makes them more aggressive and irritable. Thus, MPA nullifies the libidinous effect of estradiol in female primates. However, given estradiol and progesterone (the “bio-identical” kind) and although there was a slight decrease in the libidinous effect of estradiol, it had no side effect of increased aggression and irritability. So, we have in the female macaque, confirmation of the improvement in libido while using the estradiol and progesterone combination over estrogen plus MPA.

Another problem with synthetic progestins like MPA is that they lack the neuroprotective effects of progesterone. Progesterone reduces neuron death from cytotoxic chemicals that naturally occur in the brain. It also encourages the healing of damaged myelin that surrounds the axons of nerves. MPA not only fails to be neuroprotective, but actively suppresses the ability of the brain to biosynthesize its own progesterone that would have served as a locally neuroprotective agent. So, taking MPA is worse than using no progestin.

So why is MPA prescribed for women? Largely because of the pharmacokinetics; Progesterone has a half-life in the body of only a few hours, requiring the patient to take it twice daily, while MPA’s half-life is on the order of two to three days, making dosing easier. Why is it prescribed for MTF transsexuals? Perhaps it is a combination of ignorance of the benefits of micronized progesterone on somatic feminization and on the general lack of differentiation by primary care physicians between AGP and HSTS transsexuals? Another possibility is that primary care physicians are focusing on reduction of free testosterone in their pre-op patients and MPA has strong anti-androgen effects.

MPA and cyproterone acetate are used in “chemical castration” protocols for certain types of paraphilic sex offenders, those with courtship disorders and pedophilia. Although ethically and legally controversial, for those paraphilic sex offenders for whom reduction of libido allows rational impulse control, the reduction of recidivism is dramatic.

In pre-op transsexuals MPA alone, or in combination with cyproterone acetate (Androcur), can significantly reduce the levels of free testosterone, reducing the masculinizing effects such as body hair, head hair loss, etc. But along with the reduction of testosterone is the expected reduction of libido. For AGP transsexuals, this reduction has often been noted by clinicians to be a welcome side effect. This is likely because it reduces the intrusiveness of uncomfortable autogynephilic ideation. It is part of the now standard “transsexual myth”, promulgated by the AGP transsexual community that concerns for “gender identity” are their motivation and that sexuality, sexual motivation, plays no part in the decision making of transsexuals to transition. For transkids, this side-effect is most unwelcome, and would only be tolerated as part of the cost of reasonable somatic feminization.

Thus, for pre-op AGP transsexuals, the best course may be to continue to use MPA, as it will help reduce unwanted testosterone and reduce unwanted autogynephilic ideation.

But for pre-op transkids, prescribing estrodiol plus micronized progesterone, possibly in conjunction with cyproterone acetate, appears to be a better choice.

It would appear that for post-op transsexuals of both types, estradiol plus progesterone appears to be the best protocol. It affords maximal somatic feminization for both types, while increasing libido for the transkids and leaving the libido low for AGP transsexual, both welcome effects for each. It would be very helpful, if researchers would report results of hormonal treatments for each of the transsexual types separately to confirm or refute this early clinically observed result.

Addendum 1/12/2019:

A recent paper looking at the risk of venous thromboembolism (blood clots) and various HRT protocols has now shown that the safest is estradiol dermal patches with no increased risk over no HRT… which the worst was Premarin and MPA combination, increasing the risk by 50%.  More reason to avoid this protocol.


Marie Kwan, Judy Van Maasdam and Julian M. Davidson, “Effects of estrogen treatment on sexual behavior in male-to-female transsexuals: Experimental and clinical observations”

Johannes F. L. M. van Kemenade, Peggy T. Cohen-Kettenis, Leo Cohen and Louis J. G. Gooren, “Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals”

Karen Pazol, Mark E. Wilson and Kim Wallen, “Medroxyprogesterone Acetate Antagonizes the Effects of Estrogen Treatment on Social and Sexual Behavior in Female Macaques” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1440328/

Michael Schumacher, Rachida Guennoun, Abdel Ghoumari, Charbel Massaad, Françoise Robert, Martine El-Etr, Yvette Akwa, Krzysztof Rajkowski and Etienne-Emile Baulieu, “Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System”

John M. W. Bradford and Anne Pawlak, “Double-blind placebo crossover study of cyproterone acetate in the treatment of the paraphilias”

Barry M. Maletzkya,Gary Field, “The biological treatment of dangerous sexual offenders: A review and preliminary report of the Oregon pilot depo-Provera program”

Vinogradova, et al., “Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases”, https://doi.org/10.1136/bmj.k4810

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