Estrogen treatment is an effective alternative
Related wiki pages
Psychological Effects
I find high estrogen levels of interest from a psychological point of view
- Depression is very common in the trans community and anything that helps safely alleviate that is valuable.
- There's people working on high level estrogen for the physical benefits, but I'm not aware of anyone looking into the psychological side.
- On of the benefits of implants is that its very easy to achieve high and stable estrogen blood levels.
- When the Sydney endocrinologist Dr Jon Hayes retired there were a small but significant number of trans women who were in serious psychological distress caused by the reduction in blood levels that then followed. These numbers and symptoms seem somewhat similar cis-women suffering PMDD.
Premenstrual Dysphoric Disorder
There's very little research on trans women and a lot of the studies I've looked are related in some way relate to Premenstrual Dysphoric Disorder (PMDD) in cis-gender women. They suffer an extreme form of premenstrual syndrome (PMS), and their their treatment by the medical community reminds me in many ways of transgender women's treatment, only in some ways its even worse.
This SBS article/video describes it well, although I've heard it paints an overly positive view of the actual outcomes
Wikipedia says
Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 1.8–5.8% of menstruating women. The disorder consists of a variety of affective, behavioral and somatic symptoms that recur monthly during the luteal phase of the menstrual cycle. It affects women from their early teens up until menopause, excluding those with hypothalamic amenorrhea or during pregnancy and breastfeeding. People with PMDD are at higher risk of suicide, with rates of suicidal thoughts 2.8 times higher, history of suicidal planning 4.15 times, and suicide attempts 3.3 times.
Research
Note that these studies are on cis-women, but its important as depression and suicide risk is prevalent in the trans community. Further, some trans women suffer extreme distress on lower estrogen levels. Implants (and injections) allow very high levels to be easily achieved.
The history of supraphysiological estrogen levels and tachyphylaxis is closely tied to psychological effects of estrogen and depression.
In
Ganger 1989 when supraphysiological were found, and for which there was no known harm, their treatment consisted of
Optimal management in the cases described here is not known. There are no data to indicate that supraphysiological oestradiol concentrations cause harm. We suspect, however, that further implantation relieves symptoms for ever shortening periods. Our approach has been to withhold all forms of oestradiol until the plasma oestradiol concentration has returned to less that 200 pmol/l. This may take many months during which the patients suffer intense vasomotor and psychological symptoms, are miserable, and need much support. We then start giving them oestrogens in a form that does not cause accumulation.
Garnett 1990 rightly says of this approach
Complete withdrawl of oestrogen therapy as suggested by Ganger et al. (1989), to alow levels to return to 200 pmol/l is wrong and in severely depressed patients may be dangerous.
Supraphysiological oestradiol levels are an uncommon consequence of oestradiol implants occurring most frequently in women with a history of depression or surgical castration. These high serum oestradiol levels were not associated with any deleterious effects and may be necessary for the control of symptoms in specific women.
Garnett 1990 argues that supraphysiological levels found in the study are not tachyphylaxis
It is the increasing frequency of implantation which causes plasma oestradiol levels to rise but for selected women with severe depression or PMS these levels may be a therapeutic requirement. This is not true tachyphylaxis as these women require high oestradiol levels in order to remain symptom-free.
Garnett 1990 suggests that supraphysiological oestradiol levels may control depression. These days doctors generally won't allow supraphysiological estrogen levels, but will hand out anti-depressants like jelly beans (as if they are safer).
Summary. The serum oestradiol levels of 1388 women treated with hormone implants at a menopause clinic were reviewed in 1988. Thirty eight (3%) were found to be above 1750 pmol/l. Of these 38 women with supraphysiological oestradiol levels 23 had started therapy for menopausal symptoms and 15 for the premenstrual syndrome (PMS). Of the 23 women treated for menopausal symptoms 11 had a history of psychiatric referral for depression and nine had undergone a surgical menopause. Nine of the 15 women with PMS had a history of psychiatric referral for depressive symptoms. We conclude that the women who attain supraphysiological levels of oestradiol on implant therapy have a high frequency of psychopathology or surgical menopause and may require higher oestradiol levels for adequate control of symptoms.
Studd 1993 (page 219) says
Supraphysiological concentrations of oestradiol are probably necessary for the relief of psychological symptoms in some women, and it is reassuring that there is no evidence that such levels are dangerous.
The authors of
Garnett 1990 follow up their previous paper in a response to
Ganger 1991
Although we reported two women with high oestradiol levels after receiving 50 mg at their last implant, both had been treated for 8 years with regular larger doses (never more than 100 mg) for their depression. Both had been able to discontinue antidepressants for the first time after 10 years of previous use.
Gordon 2019 indicates this may be related to physical differences in women's brains
...one postmortem study observing that women with major depressive disorder at the time of their deaths had lower estradiol receptor α expression in the frontal cortex and hippocampus...
John Studd says
on his website in 2020 of in relation to high levels and tachyphylaxis
... There would rarely be an indication for repeat implant if the oestradiol levels are above 1000 pmol but sometimes women with convincing oestrogen responsive depression need even higher oestradiol levels and a repeat implant should not, after very careful consideration, be prohibited. It is wrong to deny women further oestrogen therapy thus making them suffer many months or years of symptoms, particularly depression, anxiety and loss of energy.
Klaiber 1979 is an early study on the effects of estrogen using very high doses of
Premarin. Note that Premarin is far more dangerous than modern bio-identical estrogens and has not been recommended for transition for many years due to the significant risks it carries.
Patients were admitted to the study only if they had an extended history (at least two years) of unsuccessful treatment by a variety of conventional therapies, eg, electroshock, antidepressant medications, psychotherapy. ... Entrance into this experimental research project was frequently viewed by the patients as a last chance to get well, after all else had failed.
... Estrogen therapy in the treated patients was begun at the dose level of 5 mg daily. The daily dosage of estrogen was increased in 5-mg steps each week that the patient failed to show improvement in the Hamilton ratings. The maximum dosage of estrogen was arbitrarily set at 25 mg daily.
... The above results indicate that high doses of oral conjugated estrogen provided significant alleviation of symptoms for a group of severely depressed women who had not responded to conventional antidepressant therapies.
... On balance, we regard this study as providing ample justification for further research into the therapeutic effects of estrogen on depression. It is important to determine now how therapeutically effective estrogen is in populations of women who are less severely ill and less resistant to therapy than the patients in our study. It is also important to know why, physiologically, some depressed women responded so much more favorably to treatment than others.
... In assessing the risk-benefit ratio of estrogen therapy with these patients, we considered several factors. Twenty five of the 40 patients (62.5%) had made serious suicide attempts prior to inclusion in the program. All of our patients expressed suicidal thoughts ranging from mild to severe during the time of the study, and a number of suicides were attempted. In addition to the suicide risk, these women faced an extremely high risk of life-long debilitation from a severe chronic depressive state. In comparison, the risks of endometrial carcinoma or thromboembolic disease seem considerably less. Thus, we feel that the risk-benefit ratio, which must be considered in the use of all drugs, is well met by this estrogen therapy.
Unfortunately following
Klaiber 1979 there was no further research. Even now, 40 years later and when safe bioidentical forms of estrogen exist, high level estrogen carries the same stigma regardless of its benefits. It's as if these fears have become
institutional memory and can no longer be questioned.
Studd 2004 refers to
Klaiber 1979 saying
The clue to the use of estrogens came with the important and somewhat eccentric paper by Klaiber and colleagues who performed a placebo controlled study of very high-dose estrogens in patients with chronic relapsing depression. They had various diagnoses and were both premenopausal and postmenopausal. They were given Premarin 5 mg daily with an increase in dose of 5 mg each week until a maximum of 30 mg/day was used. There was a huge improvement in depression on these high doses, but this work has not been repeated because of anxiety over giving high-dose estrogens.
It is estimated that up to 95% of women have some form of PMS, but, in about 5% of women of reproductive age, they will be severely affected with disruption of their daily activities. Considering these figures, it is disturbing that many of the consultations at our specialist PMS clinics start with women saying that, for many years, they have been told that there are no treatments available and that they should simply ‘live with it’.
... In spite of this clear clinical history of a woman who will probably respond to estrogens, most psychiatrists believe that such patients are ideal for the use of antidepressants.
Despite the apparent evidence that high estrogen levels protect against depression,
Panay 1997 is an example of what happens instead. This women's depression worsened and without effective help from doctors she started self-medicating with estradiol gel. By the end of the study her only effective treatment was self-medication to high estrogen levels and yet the authors refuse to consider any possibility of that being the appropriate treatment. Also note the use of the words
"claiming that her symptoms had returned", phrased in such as way as to dismiss her credibility.
A 46-year-old woman, with a past history of depression and alcoholism, was referred by her family physician complaining of severe premenstrual symptoms.
... She was maintained with 75-mg estradiol implants for 1 year. However, after the third implant posthysterectomy, she returned only 2 months later for a repeat implant, claiming that her symptoms had returned. She was not given a repeat implant at this stage because her estradiol levels were adequate at 170 pg/L.
... Despite adequate estradiol levels from unopposed estrogen, her depression and anxiety symptoms deteriorated, and she began taking haloperidol, procyclidine, and nitrazepam as prescribed by her family physician. After a while, anxiety and panic attacks became prominent and she was unable to leave the house because of agoraphobia. This was thought to be caused by side effects of the nitrazepam, which was reduced in dose.
... When she was next seen in June 1995, she stated that she had been self-medicating with estradiol gel and the day before had used half a tube. This had produced an estradiol level of 5,555 pg/L. She claimed she needed the extra estrogen because she only obtained relief of her symptoms of lack of energy, hot flushes, palpitations, and joint pains when her estrogen was "at the right level for me."
.. In December 1995, she claimed to be using eight strips of estradiol gel per day as well as her 6-monthly 50-mg implants, and her levels had declined to 634 pg/L. She felt well but was still taking antidepressants at her last visit.
References
- Gordon 2019 Estradiol Fluctuation, Sensitivity to Stress, and Depressive Symptoms in the Menopause Transition: A Pilot Study by Jennifer L. Gordon, Alexis Peltier, Julia A. Grummisch and Laurie Sykes Tottenham in 2019
- Studd 2004 Hormones and depression in women by Studd J, Panay N. in 2004, see pdf
- Panay 1997 Excessive Supraphysiologieal Levels of Estradiol due to Self-Medication and Overdosage with Estradiol Gel by Nicholas Panay and John W. W. Studd in 1997
- Studd 1993 Oestradiol and testosterone implants by Studd JW, Smith RN, in 1993
- Ganger 1991 Comment on Hormone implants and tachyphylaxis. by Gangar K, Whitehead MI.
- Klaiber 1979 Estrogen therapy for severe persistent depressions in women. by Klaiber EL, Broverman DM, Vogel W, Kobayashi Y. in 1979
Antidepressants
There's a lot more to be added here. I'd like to explore the potential risks of high estrogen levels vs the actual risks of antidepressants.
McIntyre 2005 shows how estrogen acts as an antidepressant. The 2002 publication refers to a large study, the Women's Health Initiative (WHI), which found that synthetic HRT was dangerous.
With the publication in July 2002 of results indicating potential harmful effects of HRT (estrogen monotherapy), there was a dramatic reduction in HRT prescriptions.
We found that a significant decrease in the number of HRT prescriptions was associated with a statistically significant increase in prescriptions of serotonergic antidepressants. Others have noted associations between changes in HRT and antidepressant prescription patterns.
Unfortunately, doctors will freely give out antidepressants, which have well known risks, rather than higher levels of estrogen for which there's no clear evidence of risk (or safety).
These articles are relatively easy to read and reference the original research papers. They discuss the risks and harms of antidepressants, and commercial biases in reporting and approval.
Scientific American
- The Hidden Harm of Antidepressants in 2016 - “My view is that we really don't have good enough evidence that antidepressants are effective and we have increasing evidence that they can be harmful,” Moncrieff says. “So we need to go into reverse and stop this increasing trend of prescribing [them].”
Articles on antidepressant risks in Psychology Today (
wikipedia entry)
References
