Rheumatoid Arthritis is a common autoimmune disease in the United States.
Ever since I started treating women with testosterone pellets in 2002, I have been following the benefit that testosterone pellets have on both women and men with autoimmune diseases. These patients with autoimmune diseases generally came to me for other reasons like recovering their sex drive, or regaining the ability to think and remember details, or to get their muscle mass and bone mass back, but they gave me the ability to see what testosterone pellets do to improve their autoimmune disease symptoms and how testosterone often stopped the progression of their various autoimmune diseases.
Early on in my BioBalance Health preventive medical practice I noticed the improvement in my patients who had autoimmune diseases. I was not trained with the information that testosterone pellets improved the immune status of all patients, but it clearly does! When I began to notice the transformation in this group of my patients, I started looking up research about testosterone replacement after age 40 in women with autoimmune diseases, and I found that it was actually an effective treatment for all autoimmune diseases because Testosterone modulates the immune system. If the immune system is overactive, testosterone calms it down and helps redirect it, and if it is underactive then testosterone stimulates the immune system to become normal. The physiology was obvious and it aligned perfectly with the clinical evidence I witnessed with my patients who had autoimmune diseases. As of 2026, I have spent 23 years treating thousands of patients from St. Louis, all over the US and 11 other countries. I have spent two decades observing the relationship between testosterone replacement in women with autoimmune diseases and their remarkable improvement. Let me describe some of my patients who came to me with autoimmune diseases who mystified their Rheumatologists.
First, I will discuss a patient who had Systemic Lupus (SLE). This autoimmune disease is 12 times more common in women than men and the incidence increase drastically at the time testosterone drops before menopause, after age 40.. Lupus affects almost all of the organs in the body. You may have seen a lupus rash that looks like someone’s cheeks have been slapped, but the skin becomes very sensitive to the sun too. Lupus affects the pericardium around the heart and the muscle of the heart as well. Patients with lupus can have arthritis clotting disorders and neurologic damage. The patient who taught me most about lupus was a young woman in her 40s, who had rapidly progressing lupus of the retina.
This miraculous woman with lupus had a rare form that attacked her retina. She had already gone blind in one eye when I met her, and she was rapidly going blind in the other eye. She came to me to improve her sex drive and to lose weight.
She considered her blindness inevitable even though she was seeing an ophthalmologist who gave her weekly cortisone eye injections that did not slow the progression. After her pellet insertion with testosterone, the progression of her blindness stopped abruptly! Her disease became less severe and her life improved greatly….Of course the ophthalmologist took the credit for her recovery, but it was obvious to her family and to me that the testosterone pellets stopped the autoimmune blindness from progressing. Partial blindness is disabling but it is better than total blindness.
Scleroderma is an autoimmune disease that attacks the blood vessels and collagen of the skin resulting in the inability to circulate oxygen to the skin by stiffening the capillaries and arteries. The skin becomes scarred and will not stretch. A patient with sclerodermas and toes are the first parts of the body to be affected. Raynaud’s symptoms of blue cold fingers followed by red and burning hands is sometimes the first sign that scleroderma will follow. Raynaud’s progresses to lack of blood to the extremities and the skin becomes tight, scarred and can tear.
Scleroderma is a rare autoimmune disease in the US, however I have a friend in the UK who is the President of the Scleroderma Society who has sent me quite a bit of information describing the treatments she has undergone. Her care in the UK has been stellar, and the course of her disease has been managed well. Lynn read my book when it came out in the UK and secondary to that she contacted me we became friends, pen pals, at that time. She inquired as to whether testosterone pellets might help the progression of her disease. I told her that I didn’t want to change anything she was doing but the addition of testosterone pellets with a low dose of estradiol might help her feel better and slow the progress of her Scleroderma. I found a doctor named Dr. Studd in London who gave women testosterone in pellet form like I did, and I recommended him to her. Until a few years ago she went to see him and she felt much better and felt like her disease progression had slowed.
Unfortunately, Dr Studd passed away, and she was left looking for another physician to provide her with the relief she had experienced with Testosterone and Estradiol pellets. The UK follows the US and it was not easy to get any type of hormone replacement. From 2002 (WHI study) until recently when the FDA reversed its position on replacement of estradiol. We are still looking for a doctor to help add this one bioidentical hormone to her regimen to bring back some of the health she briefly experienced with Dr. Studd.
Research Article abstracts are included at the end of this Blog.
Rheumatoid Arthritis is a common autoimmune disease in the United States. It is thought to be triggered by an abnormal immune response to a virus, but no matter how it begins, it is an inflammatory disease of the synovial lining of the joints. The immune system attacks the joint lining and destroys the joint. Hands and feet are common joints involved but any joint can be attacked. Mobility is affected, pain and inflammation that is hard to control can cause a sufferer to become completely immobile.
A young acquaintance of mine asked me if I could help his mother. She had RA and she sat in a chair all day because it hurt too much to move and her joints were stiffened and didn’t work well. I told him that I would try but she already had a Rheumatologist and I didn’t want her to change any treatment she was already getting. When I saw his mom the first time she looked twice her age. Her movement was slow as was her speech, but she was anxious to try something that could make her more mobile.
We take pictures of our patients at the first visit because I am better at remembering faces than names. The day before her second visit, after her testosterone pellet insertion, I looked at her picture and hoped she looked healthier the next day…..All I can say is what a change! She didn’t look like the same woman…her gait was normal, and she had inflection in her voice! She had done her hair, and she looked younger than her stated age now! She told me that instead of staring at the walls in her house she had painted every room and now she could play with her grandkids! I was so happy for her and it that was my last act on earth it would have been enough!
MS Multiple Sclerosis is a progressive or relapsing autoimmune disease that can progress to Death
The autoimmune target of MS is the myelin sheath that covers nerve fibers and the nerve itself. This disease can come and go and often there are months or years without symptoms, called a relapse. Patients have symptoms including loss of the ability to walk, and it affects vision and sensation.MS has only recently been categorized as an autoimmune disease; however it is treated the same way as other autoimmune disease and patients are treated with medications that shut down the immune system to try to bring a patient into remission.
The first MS patient that I treated was a 50-year-old woman dependent on a walker who had not had a remission in a long time. She came to me to improve the strength of the muscles that had not been affected by the nerve damage from the MS. She was trying her best to be independent, but she had had the disease for 10 years off and on. I gave her pellets with testosterone and lower that typical dose of estradiol.
4 months later she walked into my office with just a cane. She stood up straighter, her pain had resolved and she was very happy with her improvement, in fact her Rheumatologist felt she was in a remission secondary to the testosterone and estradiol pellets! By this time, I was confident that testosterone was the key to normalizing the workings of the immune system! Now I have many patients with autoimmune diseases.
I am aware that I have not covered all of the autoimmune diseases, however It is the same story over and over….testosterone pellets help the other drugs used to treat this group of disease to be more effective as it simultaneously improves the quality of life for these patients! In all the years I have practiced medicine (1981-2026) I have seen thousands of miracles occur for my patients by replacing testosterone with pellets, a hormone that most doctors to this day don’t admit women have at all! That is why I called my first book the Secret Female Hormone….but I was hoping that in the 10 years since the publishing that mainstream medicine would have acknowledged that women need testosterone to be healthy after age 40 and to prevent and treat the diseases that plaque us …..I am still waiting!
Scleroderma Research:
Exome sequencing link mutation in RGPD4 with systemic sclerosis-associated interstitial lung disease and the low level of testosterone—an exploration study
Na Wang1, Qian Zhang2, Wei Sun2, Xiaoyu Yang2
,
Hui Huang2 and Zuojun Xu2 *
1Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China, 2Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China Background: Interstitial lung disease (ILD) is the most common and potentially most devastating manifestation of SSc in pulmonary involvement. However, the mechanism for systemic sclerosis-associated ILD (SSc-ILD) is unclear. This work aims to explore the potential candidates for SSc-ILD upon whole exome sequencing (WES) and attempts to analyze the possible pathogenesis of SSc-
ILD from the perspective of the genetic level. Materials: Variants were con rmed by whole exome sequencing (WES), and SKAT analysis was employed to explore the most differential variants. Targeted variants were performed in biological functions, associated with clinical manifestations, and the probable change of downstream. Results: By WES and SKAT analysis of SSc with and without ILD, only the variants of RGPD4 achieved statistical power (P < 2.51 × 10-6, P-FDR = 0.025, OR = 15.95). A total of 20 rare functional variants (missense, truncating, splicing) were tested for the RGPD4 gene, and ve truncating and damaging missense variants were identi ed. Carriers showed the older inclusion age (P = 0.02) and the higher frequency use of prednisone (P=0.02) compared to the non-carriers. Further analysis illustrated that carriers showed lower levels of TES in comparison to non-carriers but did not reach statistical difference (P = 0.08). In bivariate correlation analysis, we analyzed the relationship between the mutant status of RGPD4 and the levels of sex hormones after adjusting for age confounders. Only the level of TES showed a negative correlation with the mutant status (B = -0.509, P = 0.037).
Conclusion: The variants of RGPD4 might contribute to the ILD development of SSc and might also be a causative factor of lower TES among SSc-ILD, which provided insight to a better understanding of pathobiology of SSc-ILD, and
01
Frontiers in Oncology frontiersin.orgWang et al. 10.3389/fonc.2022.956552 androgen hormone supplement might be a therapeutic target in this debilitating disease.
KEYWORDS
RGPD4, systemic sclerosis, interstitial lung disease, testosterone, whole exosome sequence
Sex hormones and sex hormone-targeting therapies in systemic sclerosis:
A systematic literature review
Jacopo Ciafa,b,c,*, Nina M. van Leeuwena, Jan W. Schoonesd, Tom W.J. Huizingaa
,
Jeska K. de Vries-Bouwstraa a Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands b Struttura Complessa di Reumatologia, Rheumatology Unit, Azienda Policlinico of Modena, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, via Pupilli 1, 40136 Bologna, Italy Walaeus Library, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
A R T I C L E Keywords:
Systemic sclerosis
Sex hormones
Androgens
Estrogens
Hormone therapy
I N F O A B S T R A C T
Background: The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women, a contribu-tion of sex hormones has been proposed. Objectives: We undertook this systematic literature review to investigate: (1) the role played by male and female sex hormones in the pathogenesis of SSc; (2) how sex hormone levels change in SSc patients and how hormonal variations modify the progression of SSc; (3) the effect of therapies targeting sex hormones on the disease course. Methods: A literature search was performed in Pubmed, Embase, Web of Science, and Cochrane library data-bases. Given the heterogeneity in study design, different quality assessment tools were applied where appropriate. Results: We retrieved 300 articles and 30 were included in the review. The available evidence points to a brogenic, but also a vasodilatory, role of estrogens in SSc. With the limitation of small sample sizes, women with SSc tend to have lower levels of androgens and non-signi cantly higher levels of estradiol compared to healthy controls, while in men we found increased levels of estradiol and discordant results for androgens. After menopause the skin score seems to decrease and prevalence of pulmonary artery hypertension seems to rise, which might be prevented by the use of hormone replacement therapy. No recent high-quality trial evaluated the efficacy of hormone-targeting therapies in SSc.
Conclusions: Few translational studies of varying quality evaluated the role of sex hormones in SSc showing possible profibrotic and vasodilatatory effects of estrogens, but more research is needed to elucidate the extent of this contribution. Insights on the influence of sex hormones, along with the availability of new compounds acting on estrogen pathways, might provide ideas for additional studies on the application of sex hormone-targeting therapies in SSc.
© 2019 Elsevier Inc. All rights reserved.
Introduction
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by vasculopathy, generalized fibrosis and deregulation of innate and adaptive immune system. The pathogene-sis is complex, multifactorial, and incompletely understood, with * Corresponding author at: Stafcentrum Reumatologie C1-R, Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The
Netherlands.
E-mail addresses: j.ciaf @lumc.nl (J. Ciaf ), [email protected]
(N.M. van Leeuwen), [email protected] (J.W. Schoones), [email protected]
(T.W.J. Huizinga), [email protected] (J.K. de Vries-Bouwstra).
https://doi.org/10.1016/j.semarthrit.2019.07.007
0049-0172/© 2019 Elsevier Inc. All rights reserved.
evidence suggesting contribution from genetic, environmental, and occupational factors [1,2]. As in most autoimmune diseases, SSc has a strong female preponderance, with women being involved between 3 and 14 times more frequently than men [1]. Moreover, clinical and immunological differences between male and female patients have been observed [3,4]. The prevalence of diffuse cutaneous SSc is higher in men [3,4], as well as cardiac involvement [3,4] and anti-topoisom-erase I antibody (ATA) positivity, while women more often present anti-centromere antibodies (ACA). One study showed that overall peripheral vascular involvement is more common in female patients than in men [4], but male patients have higher risk of developing dig-ital tip ulcers or gangrene [4]. However, contrasting results have been reported about the association between gender and digitalulcers in SSc [5]. Interstitial lung disease (ILD) prevails in men [3,4], for which it represents the leading cause of death [3,4]. In women, who have a better cumulative survival [3,4], the leading cause of death is pulmonary arterial hypertension (PAH) [3,4]. To account for the gender gap and disease dissimilarities, a role of sex hormones has been proposed [6], but few studies tried to assess their relevance in SSc, while it would be valuable, especially consider-ing that hormone pathways can be modulated. The most important sex hormones in women are estrogens, with a predominance of estradiol (E2) and estrone, respectively before and after menopause, while in men testosterone is the main androgen. Dihydrotestosterone and androstenedione are the other two important androgens, while dehydroepiandrosterone (DHEA) and the sulphated form dehydro-epiandrosterone sulphate (DHEAS) are considered as a reservoir for the production of both androgens and estrogens [7].
In men, androgen levels peak after puberty and then progressively decline with aging. In women the physiology of sex hormones is more complex and liable to high variability, especially during childbearing age, when estrogen and progesterone levels in uence, and are in uenced by, the different phases of menstrual cycle, pregnancy, and breastfeeding. Furthermore, medical interventions [8,9], genetic disorders [10], and daily life habits [11 14] can alter sex hormone levels.
Both androgens and estrogens affect the immune system and inflammation [15], have been implicated in autoimmunity, and have been reviewed in other rheumatic diseases [16,17]. Despite their putative role in SSc, their involvement has not been thoroughly explored and in particular the extent of contribution to fibrosis and
vasculopathy, the disease hallmarks, is largely unknown. The aim of this systematic literature review is to summarize the available evidence on the association of androgens and estrogens with SSc, categorizing the research question into 3 areas of interest: (1) the role of sex hormones in the pathophysiology of SSc; (2) how sex hormone levels vary in men and women with SSc compared to healthy controls and how changes in sex hormone levels modify the SSc course; (3) the effect of sex hormone-targeting therapies on SSc onset, activity, and progression.
