Post Menopausal Hair Loss and Testosterone Therapy
Susan is a 53 year old full partner in local law firm. She recently started her menopausal hormone replacement program, and has been doing well except for new onset of hair loss. She notices it during her shower when her hair sheds by the handful. Susan was quite concerned and did her own research on the internet. After this, Susan called me at the office quite sure the reason for her hair loss was the testosterone component of her hormone program causing Androgenic Alopecia. She stopped the testosterone and requested a testosterone blocking drug called spironolactone, thinking this would correct the hair loss.
Header image: Degas, Women Combing Hair 1875 Oil on Paper. Courtesy of Wikimedia commons
It is Telogen Effluvium, Not Androgenic Alopecia
I explained to Susan her hair loss is not caused by the testosterone and a testosterone blocking drug is not a good idea. The correct diagnosis is Telogen Effluvium, not Androgenic Alopecia. This can be seen shortly after starting a hormone replacement program, and usually resolves on its own after a few months. The cause is stress from hormone deficiency which is suddenly relieved by the hormone replacement. This stress causes all the hair to enter and synchronize in the Telogen phase of the hair cycle. That is why the patient will report sudden hair loss which can be demonstrated with the “Pull Test” described below. This can be understood best by looking at the cycle of hair growth (below Image)
Growth (1-2 years) Intermediate (1-2 weeks) Shedding 3-4 mo.
Above image: Cycle of Hair Growth courtesy of wikimedia commons
The Cycle of Hair Growth – There are four phases to the hair follicle cycle:
Anagen: growth phase: Lasting 3-5 years, hair growth rate is one to one and half centimeters per month, faster in summer than in winter. Full length can reach 100 cm.
Catagen: intermediate period of hair growth lasting 1-2 weeks in which hair follicles prepare to enter resting phase. In this phase, deeper portions of the hairs start to collapse getting ready for shedding. The dermal papilla at the base of the hair shaft begins to separate from the old hair follicle above it. The shedding hair is called “Club hair ” which begins to move towards skin surface, in preparation for actual shedding which occurs in next Telogen phase.
Telogen: Shedding Stage of Hair Cycle in which each hair is released and falls out. The hair follicle may remain inactive for 3-4 months, The dermal papilla is fully separated from the old hair follicle which has fallen out and a new hair shaft begins to grow from the dermal papilla at the base of the old hair follicle.
Return to Anagen: Exogen or New Anagen Phase: This is where majority of hair shedding occurs
Estrogen Controls the Hair Cycle
In 2009, Dr. M. Mancuso studied the effect of estrogen and estrogen receptors on mouse models of skin cancer, noting the skin is estrogen responsive and plays a fundamental role in hair follicle cycling. Acting through ER-beta, estrogens delay the anagen phase (initial growth phase) and lengthens the telogen phase of hair cycling. Thus, explaining the mechanism by which estrogen deficiency may induce telogen effuvian when estrogen levels are restored upon starting estrogen replacement at menopause. Dr. M. Mancuso writes:
The skin is an important estrogen-responsive tissue, and the fundamental role of estrogen in the regulation of hair follicle cycling and self-renewing is well known (31). Estrogens inhibit hair growth by delaying the initiation of anagen (i.e. phase of follicle growth) and lengthening the duration of telogen (i.e. resting phase after follicle degeneration in catagen). This was shown in early studies with ovariectomized rats (32) and by more recent work assessing the direct effect of estrogens and antiestrogens in mouse skin (33–35). The effects of estrogens are mediated by estrogen receptor (ER)-alpha and ER-beta, members of the nuclear steroid receptor superfamily. Both ERs have been detected in the skin of rodents and humans, though with distinct expression patterns (36); specifically, ER-beta has been indicated as the predominant ER in human scalp skin…(35-43)
The Pull Test Differentiates Telogen Effluvium from Androgenic Alopecia
In January 2023, Dr. Sarah Alexander Haydel discussed how common it is for women to report hair loss after first starting menopausal hormone replacement (HRT) program which includes a testosterone pellet inserted subcutaneously, delivering a fairly high dosage of testosterone. Dr. Sarah Alexander Haydel finds that all these cases of hair loss are not caused by elevated testosterone levels. Rather they are caused by telogen effluvium which can be diagnosed with a simple “pull test”. Dr. Sarah Alexander Haydel writes:
A simple “pull test” during the physical exam can help diagnosis this condition. You can lightly grab about an inch of hair with your thumb and index finger and gently pull. If more than 3-6 telogen hairs come out, this is a positive test. A telogen hair characteristically has a white bulb on the end of it…It is not uncommon to have this type of shedding after the first round of pellets in a patient that was hormone depleted…The body sees that depleted state as a stressor and once the hormones are optimized, the hair enters the anagen growing phase again and pushes out the dormant telogen hair. Reassurance to the patient that time will resolve this type of hair loss, and that the hair will be healthier and stronger in the future is important.(1)
Dr. Sarah Alexander Haydel also points out Telogen Effluvium type hair loss is “fast and furorious” wheras Androgenic Alpoecia hair loss is slow and gradual. The two entities can be can be differentiated by asking this question:
Was it [the hair loss] “fast and furious” or “slow and gradual?” This question often differentiates the two most common conditions of hair loss.(1)
Androgenic Alopecia – Miniaturized Hair
In the androgenic form of alopecia, there is progressive miniaturization of the hair shaft which is not present in telogen effluvium. Thus when the shedded hair is examined with a magnifying glass, the hair shaft diameters vary in size indicating Androgenic Alopecia. For Telogen Effluvium, the hair shaft diameters are all very uniform, the same.
The Myth that Testosterone Causes Hair Loss
Thanks to Dr. Rebecca Glaser and Dimitrakakis for their 2013 article on Testosterone therapy in women, reporting two thirds of women report hair regrowth on testosterone therapy, the anabolic effect of testosterone. They write:
There is no evidence that T [Testosterone] or T therapy is a cause of hair loss in either men or women…Hair loss is a complicated, multi-factorial, genetically determined process that is poorly understood… Hair loss is common in both women and men with insulin resistance….Approximately one third of women experience hair loss and thinning with aging, coinciding with Testosterone decline… We have previously reported that two thirds of women treated with subcutaneous T implants have scalp hair re-growth on therapy. Women who did not re-grow hair on T were more likely to be hypo or hyperthyroid, iron deficient or have elevated body mass index. In addition, none of 285 patients treated for up to 56 months with subcutaneous T therapy complained of hair loss, despite pharmacologic serum T levels on therapy… “Fact””Testosterone therapy increases scalp hair growth in women” (2)
Female Pattern Hair Loss (FPHL)/ Androgenic Alopecia
The vast majority of patients do well with testosterone replacement as noted above by Dr. Rebecca Glaser. However, rarely, a patient may report severe hair loss after starting tesotosterone replacement (FPHL) appearing as a hypersensitivity to testosterone resembling alopecia Areata (AA).
Normal Serum Androgen Levels
Surprisingly, in the majority of women with FPHL/Androgenic Alopecia, the serum serum androgen levels of testosterone and DHEA may be completely normal or even low, and these patients usually have no signs or symptoms of androgen excess (hirsutism, acne). The reality is FPHL is poorly understood by medical science. I suspect there may be a genetic component explaining the extreme variation in the patient population.
Association with Dyslipidemia, Hypercholesterolemia
For example, there may be an association of FPHL and Alopecia Areata (AA) with elevated cholesterol levels and familial hypercholesterolemia, another genetic disorder. In 2020, Dr. Megan Palmer reviews this association and suggests statin drugs may be useful, writing:
inhibition of cholesterol biosynthesis with simvastatin significantly reduced levels of sterol precursors in these animals and reversed the morphological HF [Hair Follicle] defects…increased follicular metabolism of testosterone to DHT, combined with enhanced intrafollicular steroidogenesis could be occurring…A number of studies have examined links between AGA [Androgenic Alopecia] and cholesterol levels…Recent meta‐analysis by Kim, et al[151] highlighted the association between dyslipidaemia and AGA….some studies have suggested a role for statins in reversing hair loss in certain patients. Combinations of simvastatin and ezetimibe… were found to regrow hair in patients with AA [Alopecia Areata], totalis and universalis.(25)
Hair Loss from Long Term SSRI Antidepressant Use
Hair Loss is widely known as an adverse effect of SSRI antidepressants with many case reports in the medical literature. In the menopausal female with hair loss, tapering off SSRI antidepressants will usually resolve the hair loss issues. Other adverse effects of SSRI drugs include sexual dysfunction and violent psychotic episodes. For more on this: The SSRI Antidepressant Hoax. (27-34)
Treatment of Alopecia Areata with Statin Drugs
In 2015, Dr. Carol Lattouf, University of Miami Dermatology, treated 19 Alopecia Areata patients with simvastatin and ezetimibe, finding 14 of 19 patients responded (see image below). (26)
Left Image: Fig 1. Alopecia areata. Patient #23 before (Above) and 40 weeks after (Below) treatment with simvastatin/ezetimibe. Courtesy of Lattouf, Carol, et al. “Treatment of alopecia areata with simvastatin/ezetimibe.” Journal of the American Academy of Dermatology 72.2 (2015): 359-361.
Treatment of Female Pattern Hair Loss/ Androgenic Alopecia
In 2017, Dr. Kevin Brough disclosed his treatment algorithm writing:
However, hyperandrogenism cannot be the only pathophysiologic mechanism for FPHL because the majority of women with FPHL neither have abnormal androgen levels nor do they demonstrate signs or symptoms of androgen excess (Atanaskova Mesinkovska and Bergfeld, 2013, Schmidt and Shinkai, 2015, Yip et al., 2011). Furthermore, cases have been reported in which FPHL developed in patients with complete androgen insensitivity syndrome or hypopituitarism with no detectable androgen levels (Cousen and Messenger, 2010, Orme et al., 1999). (21)
For the post-menopausal woman with FPHL, Dr. Kevin Brough advises firstly 5% Minoxidil foam for all patients, and finasteride 5 mg PO/day for the post-menopausal patients. (See Fig.2 below for treatment algorithm). Spironolactone is also useful 100-200 mg PO daily. One retrospective study of women with FPHL showed about 75% stabilization or improvement of hair loss with spironolactone. Dr. Kevin Brough writes:
[A] study of 87 pre- and postmenopausal normoandrogenic patients who were taking a 5-mg dose of finasteride per day for 12 months showed a significant increase in both hair density and thickness (Yeon et al., 2011). The effectiveness of finasteride does not seem to differ between pre- and postmenopausal patients (Yeon et al., 2011). Finasteride is classified as pregnancy category X….
Spironolactone is a potassium-sparing diuretic that functions as a competitive aldosterone antagonist and inhibits the interaction of testosterone and DHT with intracellular androgen receptors in target tissues (van Zuuren et al., 2012, Yazdabadi and Sinclair, 2011). Spironolactone also weakly inhibits androgen synthesis (Price, 2003). The anti-androgen effect is more commonly used in hirsutism and acne but has been used successfully at 100- to 200-mg daily doses to treat FPHL (Sinclair et al., 2005). One retrospective study of survey data showed that nearly 75% of women reported stabilization or improvement of their hair loss after treatment with spironolactone (Famenini et al., 2015). Similar results were obtained in an open intervention study from 2005 (Sinclair et al., 2005). While the vast majority of published data discusses adult patients, one case report described the visible improvement of FPHL in a 9-year-old patient after 6 months of therapy (Yazdabadi et al., 2009). (21)
Treatment Algorithm for Female Pattern Hair Loss
Above image Fig 2. Courtesy of Brough, Kevin R., and Rochelle R. Torgerson. “Hormonal therapy in female pattern hair loss.” International journal of women’s dermatology 3.1 (2017): 53-57. (21)
Hair Loss Products at the Compounding Pharmacy
Telogen Effluvium is usually self limited and resolves after a few months without treatment. For women wishing treatment for FPHL, topical Minoxidil is widely available usually combined with other drugs such as tretinoin, Azelaic Acid, Finasteride, progesterone and topical steroids. See the below list of available topical formulas for hair loss:
*************** Most Popular ***************************
CFS Pharmacy Hair Loss Shampoo Compounded
Fluocinonide / Azelaic Acid / Minoxidil / Tretinoin Shampoo Compounded
0.05% Fluocinonide/ 2.5% Azelaic Acid/ 2.5% Minoxidil / 0.025% Tretinoin (16)
Note: Both Tretinoin and Azelaic Acid assist with cellular turnover, but azelaic acid acts as an exfoliant and helps with bacteria and inflammation, while retinol boosts cell renewal. Both can cause skin irritation, but retinol has additional side effects like dry skin and photosensitivity (Mukherjee, 2006).May 23, 2022. Azelaic acid topical cream is used to treat mildly to moderately inflamed acne. For acne, it works by killing the bacteria that cause acne and by keeping the skin pores clean.
This is the above formula made stronger, with Finasteride/Progesterone Added, Corticosteroid removed
CFS Pharmacy Hair Loss Formulas (they also carry Niclosamide)
5% Minoxidil / 0.1%Finasteride / 5%Azelaic Acid / 0.25% Progesterone / 0.025%Tretinoin Topical Solution Compounded (19)
==================================================
******** Good Topical Foam with 3% Minoxidil/Tretinoin ***************
Minoxidil 3%/ Tretinoin 0.025% Topical Foam (17)
===========================
Shields Pharmacy Hair Loss Solution : Minoxidil 5% + Clobetasol .05% + Tretinoin .025% Compounded – Topical Solution (14)
=======================
Strut Health Mens Hair Loss Gel
Hairfect Combo: Finasteride Hair Loss Formula + StrutVite
Finasteride 0.1-0.25%, Minoxidil 0.0%-7.5%, Tretinoin 0.0%-0.0125%, Fluocinolone 0.01%
Transparent pricing 30 day supply $79 for 30 ml + 60 capsules (StrutVite) (15)
================================
New Drug Loft (NYC) Compounded formulas for Hair Loss
Before and After Photos
Below images: Female patient struggled with female pattern hair loss. A compounded solution combining minoxidil and biotin for 90 days was prescribed.
Above Images: Female patient struggled with female pattern hair loss. A compounded solution combining minoxidil and biotin for 90 days was prescribed.
Above Images: Female patient, age 42, with bald spot. The compounded solution used included Minoxidil 10%/ Cetirizine 1%/ Estradiol 0.025%/Fluocinolone 0.025%. All the above images of before and after hair loss: courtesy of New Drug Loft.
Custom-Made Compounded Medications for Hair Loss
Hair Loss formulas are formulated with the following ingredients:
Minoxidil (Rogaine) (various strengths for men and women): An antihypertensive vasodilator medication that can slow and stop hair loss and stimulate new growth. This is the only FDA-approved ingredient to treat hair loss and thinning. Known commercially as Rogaine. Can be formulated at dosages that are prescription-strength (5% and above).1
Finasteride Applied topically, finasteride yields results comparable to oral administration but without the sexual side effects.2
Estradiol and progesterone: Endogenous sex hormones that play a key role in hair loss.3
Fluocinolone: A topical steroid used to treat skin conditions such as eczema, which can impact the thickness and fullness of hair.4
Retinoic acid : Topical application of all-trans retinoic acid (tretinoin) has been shown to promote hair growth, especially when combined with minoxidil.5,6
Biotin and saw palmetto: Some small studies have shown that saw palmetto (Serenoa repens) may reduce hair loss.7,8 A combined treatment of biotin and saw palmetto has been clinically shown to decrease hair loss in both men and women.9
Proprietary biopeptide blend: Peptides have various benefits for promoting hair growth and color. GHK-Cu has been shown to increase hair follicle size,10 while Palmitoyl Tetrapeptide-20 has been shown to prevent the premature graying of hair.(18)
====================================================
Conclusion:
Thanks to Dr Rebecca Glaser for her pioneering work in testosterone for menopausal women, reporting on the myth of testosterone therapy and hair loss. For the menopausal patient concerned about hair loss, the underlying cause is most likely telegon effluvium. Howver, the occasional patient with have FPHL with normal serum androgen levels. For the woman with FPHL, treatments are available using spironolactone, or finasteride combined with Minoxidil foam or shampoo, widely availabe at compoundeing pharmacies. (21)
Why is Testosterone is an important component of our hormone replacement program? Testosterone is Breast Cancer Preventive: Mechanism of Action There are two estrogen receptors, Alpha and Beta. The Alpha receptor is pro-carcinogenic. The Beta Receptor is protective and suppresses carcinogenesis. Estradiol attaches to both receptors 50:50. Estrone (E1) attaches mostly to ER-alpha, while Estriol (E3) attaches mostly to ER Beta (protective). The most like likely mechanism for testosterone’s protective effect in breast cancer prevention is the testosterone metabolite 3β-Adiol which attaches to Estrogen Receptor Beta (ER-Beta), thus upregulated ER-Beta expression, thus inhibiting breast cancer cell growth.(38-49)
This is illustrated in 2014 by Dr. Pietro Rizzo who writes:
The two isoforms of estrogen receptor (ER) alpha and beta play opposite roles in regulating proliferation and differentiation of breast cancers, with ER-alpha mediating mitogenic effects and ER-beta acting as a tumor suppressor. …..Collectively, these data provide evidence for a novel mechanism by which activated AR [Androgen Receptor], through an up-regulation of ER-beta gene expression, inhibits breast cancer cell growth. Reference: Rizza, Pietro, et al. “Estrogen receptor beta as a novel target of androgen receptor action in breast cancer cell lines.” Breast cancer research 16 (2014): 1-13.
Articles with Related Interest:
The Lady in Grey and Hair Loss
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my blog: www.jeffreydachmd.com
=============================================
Above image: Cycle of Hair Growth courtesy of wikimedia commons
Stages of Hair Growth Courtesy of My Hair Doctor
===============================
References:
1) My Pellet Patient is Complaining of Hair Loss… Now What?
by Sarah Alexander Haydel, M.D. BioT Medical Journal: VOL1:6, Jan 17, 2023
There is no evidence that T or T therapy is a cause of hair loss in either men or women. Although men do have higher T levels than women, men are more likely to have hair loss with age. Even though women with PCOS and insulin resistance have higher T levels and commonly hair loss, this does not prove causation. Dr. Rebecca Glaser treated 285 women for a minimum of 1 year with T pellets for symptoms of androgen deficiency and were asked to complete a survey that included questions on scalp and facial hair. Two-thirds of women treated with subcutaneous T implants had scalp hair re-growth on therapy. Women who did not regrow hair on T were more likely to be hypo- or hyperthyroid, iron deficient, or have elevated body mass index. None of the patients treated complained of hair loss, despite pharmacologic serum T levels on therapy.
Moreover, in Dr. Glaser’s clinical experience of treating more than 1,100 female patients with over 10,000 subcutaneous testosterone pellet insertions, hair thinning was rarely reported. The proposed benefit of T therapy is due to the anabolic effect of it on hair growth.1,2
Hair thinning and/or hair loss is a common complaint in a doctor’s office. In the setting of a patient undergoing pellet therapy, the” knee jerk reflex” is to blame it on the pellets. Our job is to assess the patient and look for the root cause and identify any underlying disease. In the end, the main contributing factor for hair loss, regardless of pellet status, is genetics. However, stress, beauty treatments for the hair, thyroid issues, illness, medications, iron deficiency, hormone imbalance, and nutritional deficiencies are other common causes, to name a few. The first step when a patient complains of hair loss is to perform a thorough history and physical. The first question should be about the timing of the hair loss. Was it “fast and furious” or “slow and gradual?” This question often differentiates the two most common conditions of hair loss.
The fast pattern is most commonly known as telogen effluvium (TE) which is brisk shedding all over the scalp during times of stress. It often causes a high degree of concern in patients, as they can lose up to 3 times the normal amount of hair in a day. TE usually occurs several months after the inciting factor and resolves in 6-9 months after the stressor has been removed.
Pull Test for Telogen Effluvium
A simple “pull test” during the physical exam can help diagnosis this condition. You can lightly grab about an inch of hair with your thumb and index finger and gently pull. If more than 3-6 telogen hairs come out, this is a positive test. A telogen hair characteristically has a white bulb on the end of it.
It is not uncommon to have this type of shedding after the first round of pellets in a patient that was hormone depleted.
The body sees that depleted state as a stressor and once the hormones are optimized, the hair enters the anagen growing phase again and pushes out the dormant telogen hair. Reassurance to the patient that time will resolve this type of hair loss, and that the hair will be healthier and stronger in the future is important.
Androgenic Alopecia in Women-Progressive Miniaturization of Hair Follicle
The slow pattern is most commonly known as androgen alopecia (AGA) which features progressive miniaturization of the hair follicle in predisposed individuals without scarring. The incidence of AGA depends on age, sex, and ethnicity with 50 percent of white men by the age 50. In addition, 40-50% of white women will develop AGA during their lifetime. People with Asian or African ethnicity have a lower prevalence of AGA.3 The most common (pathognomonic) presentation in women is female pattern hair loss (FPHL), which is diffuse reduction in hair density affecting the mid and frontal regions of the scalp with preservation of the frontal hairline. Male-pattern balding is undoubtedly an androgen-dependent genetically determined trait. It appears that dihydrotestosterone (DHT) diminishes the anagen phase of the hair follicle by binding to androgen receptors, resulting in terminal hair transforming into thinner and shorter vellus hair over time. According to scientific studies, the tendency for hereditary hair loss is mainly transmitted through the mother via the androgen receptor (AR) on the X chromosome. As men can only inherit the X chromosome from their mother, the “risk” of suffering alopecia is more closely related to the mother or maternal grandfather than the father. However, other hereditary factors may also cause baldness and can be tested for, using saliva.
The lab workup for hair loss initially includes CBC, CMP, free T3, TPO antibodies, ferritin, B-12, total testosterone, FSH, and estradiol at minimum. I have started to add a HbA1c and fasting insulin level in some patients as insulin resistance, obesity, diabetes, and metabolic syndrome can cause hair loss in men and women. Insulin resistance and hyperinsulinemia participate in the development of AGA by producing local androgens from cholesterol and enhancing local conversion of testosterone to DHT. Obesity and insulin resistance also increases 5-alpha-reductase, which in turn increases more DHT. Age, alcohol, obesity, medications, and sedentary lifestyle increase aromatase activity, lowering T and raising E. Increased DHT, lowered testosterone, and elevated estradiol levels contribute to hair loss in genetically predisposed men and women. Hypothyroidism is associated with lower levels of sex hormone binding globulin, which may result in higher levels of free androgens that can exacerbate AGA.4
In general, treatment options should include overall health improvements such as adding a probiotic, DIM (natural DHT blocker), ADK (D3 helps hair growth), and correcting any thyroid deficiency.
Men with Androgenic Alopecia Treatment:
Specifically for men suffering from androgenic alopecia, prescription treatments were ranked in efficacy in a network meta-analysis of 23 trials. The results of this analysis indicated that 0.5mg/day of oral dutasteride had the highest probability of being the most efficacious, followed by these agents in decreasing order of efficacy: 5mg/day of oral finasteride, 5mg/day of oral minoxidil, 1mg/day of oral finasteride, 5% topical minoxidil, 2 % topical minoxidil, and 0.25mg/day of oral minoxidil5 (see Figure 1).
Female Pattern Hair Loss (Androgenic) Treatment
The efficacy of topical minoxidil (MX) alone on female pattern hair loss is limited. A study done on 120 non-menopausal women followed for 6 months showed that hair density increased the most in the 5 % minoxidil plus 12 sessions of micro-needling compared to the 5% MX plus oral spironolactone group (80-100mg daily) or the 5% MX group alone. MX is a regulator of potassium ion channels with vasodilatory effects that increase the duration of the anagen phase and induces angiogenesis surrounding hair follicles, thereby contributing to the conversion of miniaturized hairs to terminal hairs. The most common adverse events of MX include scalp pruritus and irritation. Spironolactone competitively inhibits androgen binding to intracellular receptors and is especially helpful among patients with signs of hyperandrogenism. The most common adverse effects in the Spironolactone group were menstrual disorders, hyperkalemia, and edema of the limbs though rare. In another study following 166 women for 18 months with FPHL, 74% of the patients receiving spironolactone (110 mg average daily dose) reported stabilization or improvement in their hair. Epidermal thickness and follicle diameter were increased in the micro-needling group. It has been hypothesized that the trauma generated by the needle penetration induces the release of platelet derived growth factor, epidermal growth factor, and activation of the hair matrix thru the Wnt/B-catenin pathway. Micro-punctures caused by the micro-needling may also facilitate the penetration of the topical medications6 (see figure 1).
Figure 1. Treatment Options for Hair Loss
Condition Onset 1st Line Treatment 2nd Line
Telogen effluvium (TE) Fast None/Time None/Time
Androgen Alopecia (AGA) Slow Male 0.5mg/day of oral dutasteride or 5mg/day of oral finasteride
Female Treatment: 5% Minoxidil + 12 micro-needling sessions or 5% Minoxidil + Spironolactone 80-100mg QD
In summary, hair loss is a common complaint of patients undergoing pellet therapy, thus it is important that providers understand how to evaluate and treat it. Although, testosterone therapy is often blamed for a patient’s hair loss or thinning, it is lack of hormone optimization that is more often associated with this untoward cosmetic outcome. This summary provides an overview of the two most common causes of hair loss and provides a comprehensive approach to the most effective treatments for your patients.
————————————————- –
2A) Glaser RL, Dimitrakakis C, Messenger AG. Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study. Br J Dermatolo. 2012 Feb; 166(2): 274-278.
3A) Glaser R, Dimitrakakis C. Testosterone therapy in Women: Myths and misconceptions. Maturitas. 2013; 74: 230-234.
4A) Qiu Y, Zhou X, Li Y. Systemic Review and Meta-analysis of the Association Between Metabolic Syndrome and Adrogenic Alopecia. Advances in dermatology and venerology. 2022 Dec;102:1-7.
5A) Famenini S, Slaught C, Duan L, Goh C. Demographics of women with female pattern hair loss and the effectiveness of Spironolactone therapy. J AM Acad Dermatol. October; 73(4): 704-706.
6A) Gupta AK, Venkataraman M, Talukder M, Bamimore MA. Relative Efficacy of Minoxidil and the 5-α Reductase Inhibitors in Androgenetic Alopecia Treatment of Male Patients: A Network Meta-analysis. JAMA Dermatol. 2022 Mar 1;158(3):266-274.
7A) Liang X, Chang Y, Wu H, Liu Y, Zhao J, Wang L, Zhuo F. Efficacy and Safety of 5% Minoxidil Alone, Minoxidil Plus Oral Spironolactone, and Minoxidil Plus Microneedling on Female Pattern Hair Loss: A Prospective, Single-Center, Parallel-Group, Evaluator Blinded, Randomized Trial. Front Med (Lausanne). 2022 Jul 11;9:905140.
=======================================================
2) Glaser, Rebecca, and Constantine Dimitrakakis. “Testosterone therapy in women: Myths and misconceptions.” Maturitas 74.3 (2013): 230-234.
2.5 Myth: Testosterone causes hair loss
There is no evidence that T or T therapy is a cause of hair loss in either men or women. Although men do have higher T levels than women, and men are more likely to have hair loss with age, it is unreasonable to assume that T, an anabolic hormone, causes hair loss. Hair loss is a complicated, multifactorial, genetically determined process that is poorly understood. Dihydrotestosterone (DHT), not T, is thought to be the active androgen in male pattern balding. Female ‘androgenic’ alopecia refers to a (male) pattern of hair loss in women, rather than the etiology.
Although some women with PCOS and insulin resistance have higher T levels, and do have hair loss, this does not prove causation. Hair loss is common in both women and men with insulin resistance [20
, 21]. Obesity and insulin resistance increase 5-alpha reductase, which increases conversion of T to DHT in the hair follicle [[22]]. Also, obesity, age, alcohol, medications and sedentary lifestyle increase aromatase activity, lowering T and raising E. Increased DHT, lowered testosterone, and elevated estradiol levels can contribute to hair loss in genetically predisposed men and women; as can many medications, stress and nutritional deficiencies.
Approximately one third of women experience hair loss and thinning with aging, coinciding with T decline. We have previously reported that two thirds of women treated with subcutaneous T implants have scalp hair re-growth on therapy. Women who did not re-grow hair on T were more likely to be hypo or hyperthyroid, iron deficient or have elevated body mass index. In addition, none of 285 patients treated for up to 56 months with subcutaneous T therapy complained of hair loss, despite pharmacologic serum T levels on therapy [[10]
“Fact””Testosterone therapy increases scalp hair growth in women”
====================================
******************************************************
=====================================
Female androgenetic alopecia (FAGA) VS Telogen Effluvium
3) Telogen Effluvium (Freedom Clinic Toronto)
Telogen Effluvium is a type of hair loss that occurs due to many reasons. As its name suggests, Telogen Effluvium occurs when large numbers of growing hairs suddenly enter the telogen phase, causing rapid hair loss throughout the scalp. This type of hair loss will always resolves itself, even when the cause is unknown, but only when the cause is removed. TE can be caused by physical or emotional stress. Physical stressors can include medication changes, surgery, a fever, hormonal imbalances, nutritional changes, etc. The hair loss usually occurs about 3 months after the stressful event, and will begin to resolve itself about 3 months after the resolution of the event, or once the cause has been removed.
Our advanced trichological analyses can help you determine the type and cause of your hair loss, and therefore steer you on a more correct and appropriate path for treatment. It is important to remember that all hair loss treatments are designed to treat specific types of hair loss, so what works in one person may not work in another. It is always best to undergo a full analysis with a certified trichologist before pursuing any treatment protocol.
4) Telogen Effluvium on Drugs.com
Simple Diagnosis of Telogen Effluvium
If the doctor gently tugs on some hairs on your scalp and four or more hairs come out, you probably have telogen effluvium. Also, the hairs will look like hairs in the telogen phase — they will have a white bulb at the end that was in the scalp, and will not have a gel-like covering around that end of the hair
In cases where hair growth has not returned to a satisfactory level, your doctor may prescribe minoxidil (Rogaine), a lotion applied to the scalp that may stimulate hair growth in some people.
The outlook for telogen effluvium is very good. Most cases run their course within six to nine months, and the hair usually grows back.
The white bulb commonly seen with shed hair is actually keratin, or dead skin, with the hair follicle remaining in place to regrow a new hair strand.
5) https://www.aafp.org/pubs/afp/issues/2017/0915/p371.html
Phillips, T. Grant, W. Paul Slomiany, and Robert Allison. “Hair loss: common causes and treatment.” American family physician 96.6 (2017): 371-378.
!!!!!!!!! Nice images !!!!!!!!!
pdf
6) Cardoso, Camila O., et al. “Topical treatment for scarring and non-scarring alopecia: An overview of the current evidence.” Clinical, Cosmetic and Investigational Dermatology (2021): 485-499.
=============================================
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
Good Images
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
hair diameter diversity (HDD),
Female androgenetic alopecia (FAGA) VS Telogen Effluvium
7) Bains, Pooja, Simplepreet Kaur, and Komalpreet Kaur. “Comparison of dermoscopic findings in female androgenetic alopecia and telogen effluvium and female controls in a tertiary care center.” The Journal of Clinical and Aesthetic Dermatology 15.5 (2022): 29.
Female androgenetic alopecia (FAGA) is a patterned hair loss caused by progressive miniaturization of hair follicles. This leads to reduction in the number and thickness of hairs, especially in the central, frontal, and parietal scalp regions. Telogen effluvium (TE) is characterized by diffuse hair loss within months of a significant systemic stressor because of premature follicular transition from the anagen to the telogen.
This article highlights the dermoscopic differences between TE, FAGA ,and its comparison to healthy female controls. These dermoscopic features will help in difficult to differentiate cases. Dermoscopy of scalp has proven its worth by reducing the need of biopsy. It helps in detecting FAGA on the basis of increased proportion of thin and vellus hairs, hair diameter diversity, perifollicular discoloration, and the presence of a variable number of yellow dots. The clinical diagnosis of FAGA augmented by the dermoscopic signs allows timely treatment before the occurrence of significant reduction in hair volume.
Limitations. Biopsies were not performed in every patient as the diagnosis was evident clinically in many patients and an invasive procedure seemed unwarranted.
Telogen effluvium (TE) is another leading cause of female hair loss but it is a self-limiting process and almost never causes obvious baldness, whereas FAGA progresses in time, leading to a significant decrease in hair thickness. It is often difficult to distinguish FAGA from TE, especially in the early stages.
Vellus hair is thin, fine hair that grows on most of your body. You might know it as “peach fuzz.” It’s different from the thicker, longer hair you have on your scalp, which healthcare providers call terminal hair. Vellus hair is usually lighter and shorter than terminal hair.
===================================
8) Rebora, Alfredo, et al. “Distinguishing androgenetic alopecia from chronic telogen effluvium when associated in the same patient: a simple noninvasive method.” Archives of dermatology 141.10 (2005): 1243-1245.
We propose a simple and noninvasive method to accomplish this, based on the concept that vellus hairs have their own telogen phase that results in the extrusion of a shorter telogen hair. As AGA is determined by the increasing number of vellus hair, detecting a high number of telogen vellus hairs is likely to be a good measure of AGA, and vice versa; their low number in the presence of important hair shedding may indicate CTE.
Patients complaining of hair loss shed telogen hairs with different lengths and diameters. When patients appear to have AGA, they shed shorter and thinner telogen hairs owing to miniaturization. When hairs are 3 cm or shorter, they are called vellus hairs,2 and their number may serve as a diagnostic tool for AGA. We assumed that 10% or more of them were enough to consider the diagnosis of AGA.3
======================================
Features of Androgenic Hair Loss in Women (diffuse thinning at the crown with a presenting concern of a widening center hair part)
Topical Minoxidil
9) Castellanos, Amber, et al. “63-Year-Old Female with Diffuse Thinning of the Hair.” Clinical Cases in Alopecia. Cham: Springer International Publishing, 2023. 1-9.
Androgenetic alopecia (AGA) is a form of non-scarring alopecia caused by an excessive response to androgens. It is the most common type of progressive hair loss in both men and women, affecting up to 80% of men and 50% of women over the course of their life. Presentations of AGA differ between sexes with men initially experiencing recession of the frontal hairline and increased loss in the temporal regions.
In women, the hair loss consists of diffuse thinning at the crown with a presenting concern of a widening center hair part. AGA is a hormonally driven hair loss where androgens may have a paradoxical effect on some areas of the scalp and cause dark terminal hair follicles to regress to fine and colorless vellus hairs. Not only do androgens cause hair follicle regression into vellus hairs, but they also shorten the anagen (growth) phase. This results in a smaller anagen-to-telogen ratio and ultimately leads to follicular shrinkage and a decrease in overall hair coverage on the scalp. Diagnosis of AGA is based on a thorough history and physical exam. Biopsy is rarely required for diagnosis but if performed, shows pronounced miniaturization of hair follicles and complete zones of replacement of terminal hair by vellus hair. Treatment of AGA focuses on increasing scalp coverage as well as impeding the progression of hair thinning. This can be achieved through the use of topical minoxidil for both men and women. The use of oral finasteride may be utilized in men and recent studies suggest its use in non-reproductive females. Females may also use oral spironolactone as an alternative therapy to finasteride. Recent studies are investigating the use of platelet-rich plasma, low-level laser therapy, and janus-kinase inhibitors for the treatment of AGA with promising preliminary results.
=================================
10) Meher, Arpita, et al. “Hair loss–A growing problem among medical students.” Cosmoderma 3 (2023).
Good Images
Figure 1:Types of hair loss.
MEDICATION: There are currently two medications authorized for the treatment of hair loss in men: Oral finasteride and topical minoxidil. Both medications affect the hair-growth cycle and lengthen existing hair, enhancing scalp coverage, and preventing additional hair loss in the vertex and frontal areas. However, neither medication fully regrows hair nor response to treatment is same among individuals. The treatment duration is typically 6–12 months. Finasteride reduces the conversion of testosterone to dihydrotestosterone by acting as a competitive inhibitor of Type 2 5’-reductase, and a daily dosage of 1 mg is safe and well tolerated. Minoxidil encourages hair growth by lengthening the anagen phase and enlarging underdeveloped and miniature follicles. The majority of side effects from topical minoxidil are dermatological, including scalp irritation and hypertrichosis.
====================================================
11) Ramos, Lya Duarte, et al. “Dermoscopic findings in female androgenetic alopecia.” Anais brasileiros de dermatologia 87 (2012): 691-694.
BACKGROUND: Androgenetic alopecia is the most common form of hair loss. It is a clinical entity of relevant interest and presents a significant psychosocial impact as it undermines self-esteem and quality of life in female patients due to the importance of the hair for people’s facial balance. OBJECTIVE: The purpose of the present study is to evaluate dermoscopic signs in women clinically diagnosed with androgenetic alopecia. METHOD: Observational study with 34 women between 17 and 68 years old who were diagnosed with androgenetic alopecia. All of them underwent photographic sessions with a 10x magnification dermoscope and a digital camera zoom set to 20x magnification and 40x magnification on the scalp frontal midline. RESULTS: All patients showed miniaturization. A peripilar brown halo was found in 22 patients, honeycomb-like scalp pigmentation was found in 14 and yellow dots in only 1 patient. Recent studies show dermoscopy as the new tool for diagnosis assistance and treatment follow up in scalp disorders. Our study used an ordinary dermoscope and we evaluated several findings reported in the literature with significant clarity and easiness. CONCLUSION: The dermoscope, which is used by dermatologists on a daily basis, is an excellent tool to assist in early diagnosis and assessment of therapeutic response in androgenetic alopecia.
============================================
12) Bittencourt, C., et al. “Chronic telogen effluvium and female pattern hair loss are separate and distinct forms of alopecia: a histomorphometric and immunohistochemical analysis.” Clinical and experimental dermatology 39.8 (2014): 868-873.
Chronic telogen effluvium (CTE), a poorly understood condition, can be confused with or may be a prodrome to female pattern hair loss (FPHL) [androgenic type]. The pathogenesis of both is related to follicle cycle shortening and possibly to blood supply changes.
Aim: To analyze a number of histomorphometric and immunohistochemical findings through vascular endothelial growth factor (VEGF), Ki‐67, and CD31 immunostaining in scalp biopsies of 20 patients with CTE, 17 patients with mild FPHL and 9 controls.
Methods: Ki‐67 index and VEGF optical density were analyzed at the follicular outer sheath using ImageJ software. CD31 microvessel density was assessed by a Chalkley grid.
Results: Significant follicle miniaturization and higher density of nonanagen follicles were found in FPHL, compared with patients with CTE and controls. Ki‐67+ index correlated positively with FPHL histological features. The FPHL group showed the highest VEGF optical density, followed by the CTE and control groups. No differences were found in CD31 microvessel density between the three groups.
Conclusions: Histomorphometric results establish CTE as a distinct disorder, separate from FPHL from its outset. Its pathogenic mechanisms are also distinct. These findings support the proposed mechanism of ‘immediate telogen release’ for CTE, leading to cycle synchronization. For FPHL, accelerated anagen follicular mitotic rates and, thus, higher Ki‐67 and VEGF values, would leave less time for differentiation, resulting in hair miniaturization.
============================================
!!!!!!!!!!!!!!!!!!!!!!!!
Good Images !!!!!!!!!!!!!!!!!!!!!!!!
13) Rossi, Alfredo, et al. “Clinical and trichoscopic graded live visual scale for androgenetic alopecia.” Dermatology Practical & Conceptual 12.2 (2022).
In both sexes, AGA [androgenic alopecia] is characterized by progressive miniaturization of hair follicles and evolution of terminal hairs to vellus hairs.
We took macroscopic photographs of each patient’s scalp using a video-dermoscope (FotoFinder®). The instrument was attached to a rotating arm of a head-positioning device (Canfield Scientific®) in order to take pictures in standardized areas of the scalp: 2 for men (frontal and vertex region) and 1 for women (only frontal region). The scalp of all subjects was combed along the midline to the sides and evaluated using the video-dermoscope. Digital trichoscopic photographs were obtained in standardized scalp areas according to patient sex: in women, photographs were collected in the scalp point corresponding to the intersection between the line connecting the ears and the line connecting the tip of the nose and the vertex (“P point”). In men, photographs were collected at the vertex (“V point”) and 2 centimeters ahead of the intersection point previously described for women (“F point”). These images were taken at 20-fold magnification, which allows high-quality enlargement of a 0.903 cm2 area (field of view).
All the 122 trichoscopic pictures were analyzed with Trichoscale Pro® software, which allows to perform accurate automatic measurements of scalp structures, with subsequent manual verification.
=======================================================
14) Shields Pharmacy Hair Loss Solution
Minoxidil 5% + Clobetasol .05% + Tretinoin .025% Compounded – Topical Solution
=======================
15) Strut Health Mens Hair Loss Gel
Hairfect Combo: Finasteride Hair Loss Formula + StrutVite
Finasteride 0.1-0.25%, Minoxidil 0.0%-7.5%, Tretinoin 0.0%-0.0125%, Fluocinolone 0.01%
Transparent pricing 30 day supply $79 for 30 ml + 60 capsules (StrutVite)
16) CFS Pharmacy Hair Loss Shampoo Compounded
Fluocinonide / Azelaic Acid / Minoxidil / Tretinoin Shampoo Compounded
$59.95 SKU fluocinonide-azelaic-acid-minoxidil-tretin
Minoxidil 3%/ Tretinoin 0.025% Topical Foam
—————————————————-
18) New Drug Loft (NYC) Compounding for Hair Loss: Hair loss and thinning can be a difficult diagnosis for men and women. We create custom non-surgical solutions backed by science to support all patient needs.
Before and After Photos
Female patient struggled with female pattern hair loss. A compounded solution combining minoxidil and biotin for 90 days was prescribed.
Female patient, age 42, with bald spot. The compounded solution used included Minoxidil 10%/Cetirizine 1%/Estradiol 0.025%/Fluocinolone 0.025%.
Custom-Made Compounded Medications for Hair Loss
Our easy-to-use formulas integrate easily into daily routines and address these variables by offering a prescriber the ability to formulate a multi-phasic compound with ingredients such as:
Minoxidil (various strengths for men and women): An antihypertensive vasodilator medication that can slow and stop hair loss and stimulate new growth. The only FDA-approved ingredient to treat hair loss and thinning. Known commercially as Rogaine. Can be formulated at dosages that are prescription-strength (5% and above).1
Finasteride Applied topically, finasteride yields results comparable to oral administration but without the sexual side effects.2
Estradiol and progesterone: Endogenous sex hormones that play a key role in hair loss.3
Fluocinolone: A topical steroid used to treat skin conditions such as eczema, which can impact the thickness and fullness of hair.4
Retinoic acid : Topical application of all-trans retinoic acid (tretinoin) has been shown to promote hair growth, especially when combined with minoxidil.5,6
Biotin and saw palmetto: Some small studies have shown that saw palmetto (Serenoa repens) may reduce hair loss.7,8 A combined treatment of biotin and saw palmetto has been clinically shown to decrease hair loss in both men and women.9
Proprietary biopeptide blend: Peptides have various benefits for promoting hair growth and color. GHK-Cu has been shown to increase hair follicle size,10 while Palmitoyl Tetrapeptide-20 has been shown to prevent the premature graying of hair.11
19) CFS Pharmacy Hair Loss Formulas (also carry Niclosamide)
Minoxidil / Finasteride / Azelaic Acid / Progesterone / Tretinoin Topical Solution Compounded $84.95 SKU
20) Tretinoin in Hair Loss Formulas June 27th, 2023
Samual Abiola Pharm.D. Candidate 2024 Philadelphia College of Pharmacy
Tretinoin is a retino l(vitamin A derivative) that is used to treat skin issues like acne and wrinkles. However, it is now showing promise in treating hair loss as well.
=============================================
Female Pattern Hair Loss – Androgenic Alopecia
21) Brough, Kevin R., and Rochelle R. Torgerson. “Hormonal therapy in female pattern hair loss.” International journal of women’s dermatology 3.1 (2017): 53-57.
However, hyperandrogenism cannot be the only pathophysiologic mechanism for FPHL because the majority of women with FPHL neither have abnormal androgen levels nor do they demonstrate signs or symptoms of androgen excess (Atanaskova Mesinkovska and Bergfeld, 2013, Schmidt and Shinkai, 2015, Yip et al., 2011). Furthermore, cases have been reported in which FPHL developed in patients with complete androgen insensitivity syndrome or hypopituitarism with no detectable androgen levels (Cousen and Messenger, 2010, Orme et al., 1999).
finasteride
Another study of 87 pre- and postmenopausal normoandrogenic patients who were taking a 5-mg dose of finasteride per day for 12 months showed a significant increase in both hair density and thickness (Yeon et al., 2011). The effectiveness of finasteride does not seem to differ between pre- and postmenopausal patients (Yeon et al., 2011). Finasteride is classified as pregnancy category X.
dutasteride
A study of women after 3 years of therapy showed that dutasteride may be more effective than finasteride in women under 50 years of age as measured by hair thickness (not hair density) at the center and vertex scalp (Boersma et al., 2014). One case report of a 46-year-old female with FPHL showed some response after 6 months of treatment with a dose of 0.5-mg dutasteride daily despite a minimal response to treatment with finasteride and minoxidil (Olszewska and Rudnicka, 2005). Data with regard to the treatment side effects in women is extremely limited. Dutasteride is classified as pregnancy category X because of teratogenicity and should have the same theoretical risk of breast cancer as mentioned in relation to finasteride (Kelly et al., 2016).
Spironolactone
Spironolactone is a potassium-sparing diuretic that functions as a competitive aldosterone antagonist and inhibits the interaction of testosterone and DHT with intracellular androgen receptors in target tissues (van Zuuren et al., 2012, Yazdabadi and Sinclair, 2011). Spironolactone also weakly inhibits androgen synthesis (Price, 2003). The anti-androgen effect is more commonly used in hirsutism and acne but has been used successfully at 100- to 200-mg daily doses to treat FPHL (Sinclair et al., 2005). One retrospective study of survey data showed that nearly 75% of women reported stabilization or improvement of their hair loss after treatment with spironolactone (Famenini et al., 2015). Similar results were obtained in an open intervention study from 2005 (Sinclair et al., 2005). While the vast majority of published data discusses adult patients, one case report described the visible improvement of FPHL in a 9-year-old patient after 6 months of therapy (Yazdabadi et al., 2009).
The role of estrogen and progestogen drugs in the treatment of hair loss and growth is also unclear… Estrogen has been hypothesized to have a protective role against hair loss on the basis of the observation that patients with lower estrogen levels during menopause, postpartum, or treatment with aromatase inhibitors or selective estrogen receptor modulators are more likely to develop FPHL (Atanaskova Mesinkovska and Bergfeld, 2013, Park et al., 2014).
topical minoxidil 5% foam daily.
Our practice approach is depicted in Figure 2. All patients, unless contraindicated, initiate therapy with topical minoxidil 5% foam daily. This is the only therapy that is approved by the FDA for FPHL and has been shown to be safe and effective (van Zuuren et al., 2016, Varothai and Bergfeld, 2014).
Additionally, two other considerations are important for a patient who receives treatment for FPHL. First, there is a set of reasonable expectations in patients. Maintaining the current hair density can be considered a successful treatment because women tend to have further thinning as they age (Harfmann and Bechtel, 2015). Second, it is important to ensure that patients understand that progress is slow, and months or years can be required to see a significant improvement (Boersma et al., 2014, Yeon et al., 2011). In our practice, we wait at least 6 months to assess treatment efficacy.
FPHL is common and can be distressing for patients. Further, treatment of FPHL can be long and difficult and what patients hope for or expect are not always the same as what clinicians consider successful therapy. However, patients are often appreciative as you partner with them to treat this frustrating disease.
22) Yeon, J. H., et al. “5 mg/day finasteride treatment for normoandrogenic Asian women with female pattern hair loss.” Journal of the European Academy of Dermatology and Venereology 25.2 (2011): 211-214.
Background: Various treatments have been attempted for female pattern hair loss (FPHL), including topical minoxidil, oral antiandrogen and finasteride. But, there is no consensus on the standard treatment options. Clinical efficacy of finasteride in treating FPHL is still in controversy, but there is a tendency to high dose finasteride, which is more effective than lower dose.
Objectives: The purpose of this study was to evaluate the clinical efficacy of high dose (5 mg/day) oral finasteride in normoandrogenic Asian women with FPHL.
Methods: Total of 87 normoandrogenic, pre and post-menopausal women with FPHL were enrolled in this study. They were treated with oral finasteride (Proscar(®)), 5 mg daily for 12 months. Efficacy was evaluated with hair density and thickness changes assessed by phototrichogram and global photographs using 7-point scale.
Results: Eighty-six patients completed 12 months of finasteride treatment schedule. One patient (1.1%) withdrew due to headache. At initial visits, mean hair density was 90 ± 22/cm(2) and mean hair thickness was 64 ± 11 μm. After 12 months of finasteride treatment, hair density was significantly increased to 107 ± 23/cm(2) (P<0.001), and hair thickness was also significantly increased to 70 ± 9 μm (P=0.02). In global photographs, 70 (81.4%) of the 86 patients were improved (57 were slightly, 10 were moderately and four were greatly improved). Patients without any changes were 13 (15.1%) and 3 (3.5%) patients reported slightly aggravated. Four patients (4.6%) reported adverse events (headache, menstrual irregularity, dizziness and increased body hair growth). However, these adverse events were mild and disappeared soon.
Conclusions: Oral finasteride, 5 mg/day, may be an effective and safe treatment for normoandrogenic women with FPHL.
23) Bhat, Yasmeen Jabeen, Insha Latif, and Iffat Hassan. “Female pattern hair loss—An update.” Indian Dermatology Online Journal 11.4 (2020): 493-501.
24) Seyed Jafari, S. Morteza, et al. “Safety of Antiandrogens for the Treatment of Female Androgenetic Alopecia with Respect to Gynecologic Malignancies.” Journal of Clinical Medicine 13.11 (2024): 3052.
25) Palmer, Megan A., et al. “Cholesterol homeostasis: Links to hair follicle biology and hair disorders.” Experimental dermatology 29.3 (2020): 299-311.
Associations have been made between sterol levels and certain hair disorders, and lipid‐modulatory drug therapies have been reported to cause both hair loss and hair growth.[
Of relevance to this is evidence suggesting that frontal fibrosing
alopecia (FFA), a form of PCA primarily observed in women, may be
linked to sex steroid responses.[87] Indeed, postmenopausal decline
in DHEA/estrogen activity or levels may predispose individuals to
FFA development
Supporting this, inhibition of cholesterol biosynthesis with simvastatin significantly reduced levels of sterol precursors in these animals and reversed the morphological HF defects.
increased follicular metabolism of testosterone to DHT, combined
with enhanced intrafollicular steroidogenesis could be occurring
A number of studies have examined links between AGA and cholesterol
levels, in particular focusing on cardiovascular disease risk[136‒143] and
metabolic syndrome.[136,144‒150] Recent meta‐analysis by Kim, et al[151] highlighted the association between dyslipidaemia and AGA. The findings show significant increases in both total cholesterol and LDL levels, coupled to lower HDL, though the picture for HDL is less clear with some individual case studies reporting no changes or only small, non‐significant reductions in HDL.[137‒140,143‒145,150,152] Total cholesterol and LDL levels were more consistently increased across the studies.
Can statins impact on hair loss? Statins, a class of drug used to lower serum cholesterol levels through inhibition of HMGCR, have come under close scrutiny for the treatment of certain alopecias, as well as reports that they may in themselves cause hair loss.
Juxtaposed to this, some studies have suggested a role for statins
in reversing hair loss in certain patients. Combinations of simvastatin
and ezetimibe (commonly used to block Niemann‐Pick C1‐like
1‐mediated uptake of dietary cholesterol when treating hypercholesterolaemia) were found to regrow hair in patients with AA, totalis and universalis.[17] It should be stated that this case study[17] was not a randomised control trial and care should be taken in interpreting
these observations, considering the potential for spontaneous regrowth
in this disorder. Indeed, the extent of regrowth in response to this therapy varies significantly between studies, ranging from <20% to ‘significant’,[16‒19] with patients displaying more severe AA receiving no benefit.[183,184]
26) Lattouf, Carol, et al. “Treatment of alopecia areata with simvastatin/ezetimibe.” Journal of the American Academy of Dermatology 72.2 (2015): 359-361.
Fig 1. Alopecia areata. Patient 23 before (A) and 40 weeks after (B) treatment.
Long term use of antidepresants and alopecia.(27-34)
27) Hedenmalm, Karin, Anders Sundström, and Olav Spigset. “Alopecia associated with treatment with selective serotonin reuptake inhibitors (SSRIs).” Pharmacoepidemiology and drug safety 15.10 (2006): 719-725.
28) Pejcic, Ana V., and Vikash Paudel. “Alopecia associated with the use of selective serotonin reuptake inhibitors: systematic review.” Psychiatry Research 313 (2022): 114620.
29) Mercke, Yekaterina, et al. “Hair loss in psychopharmacology.” Annals of clinical psychiatry 12 (2000): 35-42.
30) Hekmatjah, Joshua, Kinza Tareen, and Ruqiya S. Tareen. “Citalopram-Associated Alopecia: A Case Report and Brief Literature Review.” Current Drug Safety 14.2 (2019): 167-170.
31) Kurhan, Faruk, and Gülsüm Zuhal KAMIŞ. “Hair loss associated with paroxetine use: A case report.” Turk Psikiyatri Dergisi 32.1 (2021): 61.
32) Turkoglu, Serhat. “Fluoxetine-and sertraline-related hair loss in a teenager: a case report.” Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology 23.1 (2013): 77-80.
33) Kıvrak, Yüksel, et al. “Diffuse hair loss induced by sertraline use.” Case reports in psychiatry 2015.1 (2015): 703453.
34) Alhomaid, Mohammed Hasan. “Escitalopram induced hair loss.” Ann Clin Psychiatry 12 (2016): 35-42.
ER-Beta (Estriol-ER-Beta) (Premarin B-Ring Steroids ER-Beta) (Prometrium downregulates ER Alpha) (Androgens – 3BetaDiol)
35) Mancuso, M., et al. “Modulation of basal and squamous cell carcinoma by endogenous estrogen in mouse models of skin cancer.” Carcinogenesis 30.2 (2009): 340-347.
The skin is an important estrogen-responsive tissue, and the fundamental role of estrogen in the regulation of hair follicle cycling and self-renewing is well known (31). Estrogens inhibit hair growth by delaying the initiation of anagen (i.e. phase of follicle growth) and
lengthening the duration of telogen (i.e. resting phase after follicle degeneration in catagen). This was shown in early studies with ovariectomized rats (32) and by more recent work assessing the direct effect of estrogens and antiestrogens in mouse skin (33–35). The
effects of estrogens are mediated by estrogen receptor (ER)-a and ERb, members of the nuclear steroid receptor superfamily. Both ERs have been detected in the skin of rodents and humans, though with distinct expression patterns (36); specifically, ERb has been indicated as the predominant ER in human scalp skin (37), whereas in murine skin both ERs are expressed during hair follicle cycling in hair cycle-dependent manner (38).
These and previous data from studies in rodents (30) suggest that estrogens may be key modulators of skin tumorigenesis. The effects of estrogens are mediated by estrogen receptor (ER)-a and ERb, members of the nuclear steroid receptor superfamily. Both ERs have been detected in the skin of rodents and humans, though with distinct expression patterns (36); specifically, ERb has been indicated as the predominant ER in human scalp skin (37), whereas in murine skin both ERs are expressed during hair follicle cycling in hair cycle-dependent manner (38).
In ovariectomized Ptch1þ/ and Car-S females, basal and squamous tumor induction were drastically increased over intact controls (CNs), and restored to levels observed in males, showing that endogenous estrogens play a critical role in protection against BCC and SCC carcinogenesis by diverse agents in mouse skin.
The skin locally synthesizes significant amounts of sexual hormones with intracrine or paracrine actions. However, the local level of each sexual steroid depends on the expression of androgen-and estrogen-synthesizing enzymes in different cell types (50). The role of estrogen in the regulation of hair follicle cycling in mice was rediscovered in the past decade, following a seminal paper by Oh et al. (33), showing that an ER pathway within the dermal papilla regulates the telogen–anagen follicle transition and that 17-b-estradiol blocks hair growth and arrests hair follicles in telogen.
Experimental data from the present study support the concept that
female sex hormones can be protective in non-melanoma skin carcinogenesis; in fact, we found that skin tumor development was significantly enhanced after ovarian hormone withdrawal in two independent experimental models. The results shown here demonstrate increased skin tumor incidence and multiplicity and decreased tumor latency in ovariectomized versus CN females, regardless of the nature of the keratinocyte-initiating agent (i.e. chemical for SCC and physical for BCC). Remarkably, malignant progression of benign papillomas to SCC occurred almost exclusively in OVX Car-S and was rare in CN females following two-stage carcinogenesis by DMBA/TPA.
To shed light on potential mechanisms involved in estrogen modulation of skin tumor progression, we examined ER protein levels in benign skin papillomas from the different Car-S groups. Immunoblots of papilloma extracts showed significantly increased expression of ERa and downregulation of ERb in tumors from OVX relative to
CN tumors, suggesting a role of the ratio ERa:ERb in susceptibility of skin to estrogen-modulated carcinogenesis, and a correlation of decreased ERb expression with increased malignant progression of initially benign papillomas in ovariectomized Car-S mice.
Previous studies have established a complex relationship between ERs and cyclin D1, with important implications for proliferation of estrogen-responsive tissues and deregulation of proliferation in cancer (42,43). To further explore this issue, we analyzed tumors for expression of cyclin D1, which among D-type cyclins controlling cell cycle regulation has been most directly implicated in oncogenesis. In the presence of estrogen, cyclin D1 is one important target gene through which estrogen-complexed ERa mediates its proliferative action, whereas estrogen-complexed ERb represses cyclin D1 gene transcription and blocks ERa-mediated induction when both receptors are present (56).
In the absence of estrogen, however, cyclin D1 is able to bind to and activate transcription mediated by ER-alpha (42,43,57). Significantly, we detected cyclin D1 upregulation in tumors from OVX relative to CN mice. Thus, our results suggest that in tumors from intact mice, where the ratio ERa:ERb is low, the protective role of ER-beta may be privileged over the proliferation stimulus mediated by the a-isoform, whereas in tumors from ovariectomized animals, the inverted ERa:ERb ratio may favor proliferation and malignant progression, possibly due to the oncogenic role of cyclin D1. This hypothesis is supported by the higher proliferation rate observed in papillomas from OVX compared with intact CN mice, a finding also observed in ER-positive breast cancer, where high cyclin D1 expression correlates with high Ki67 expression (58). We cannot exclude, however, that ovariectomy may modulate other factors involved in the regulation of skin development and functions, such as progesterone levels (59) and that this modulation may in turn influence tumor development.
In summary, our study shows for the first time a protective role of endogenous estrogen against basal and squamous skin tumorigenesis caused by physical or chemical agents in independent mouse models Finally, our study suggests that reciprocal expression of ERa and ERb may be associated with estrogen-mediated modulation of squamous epithelial carcinogenesis, with a key role played by cyclin D1.
36) Thornton,M.J. (2002) The biological actions of estrogens on skin. Exp.
Dermatol., 11, 487–502.
37) Johnson,E. (1958) Quantitative studies of hair growth in the albino rat. II.
The effect of sex hormones. J. Endocrinol., 16, 351–359.
38) Oh,H.S. et al. (1996) An estrogen receptor pathway regulates the telogenanagen
hair follicle transition and influences epidermal cell proliferation. Proc. Natl Acad. Sci. USA, 93, 12525–12530.
39) Smart,R.C. et al. (1999) Effects of 17-beta-estradiol and ICI 182 780 on
hair growth in various strains of mice. J. Investig. Dermatol. Symp. Proc., 4,
285–289.
40) Chanda,S. et al. (2000) 17Beta-estradiol and ICI-182780 regulate the hair
follicle cycle in mice through an estrogen receptor-alpha pathway. Am. J.
Physiol. Endocrinol. Metab., 278, E202–E210.
41) Ohnemus,U. et al. (2006) The hair follicle as an estrogen target and source.
Endocr. Rev., 27, 677–706.
42) Thornton,M.J. et al. (2003) Oestrogen receptor beta is the predominant
oestrogen receptor in human scalp skin. Exp. Dermatol., 12, 181–190.
43) Ohnemus,U. et al. (2005) Hair cycle control by estrogens: catagen induction
via estrogen receptor (ER)-alpha is checked by ER beta signaling.
Endocrinology, 146, 1214–1225.
================================
===============================================
Hair follicle-en.svg
From Wikimedia Commons, the free media repository
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my blog: www.jeffreydachmd.com
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit by Jeffrey Dach MD
Heart Book by Jeffrey Dach MD
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com
www.drdach.com
Click Here for: Dr Dach’s Online Store for Pure Encapsulations Supplements
Click Here for: Dr Dach’s Online Store for Nature’s Sunshine Supplements
Web Site and Discussion Board Links:
jdach1.typepad.com/blog/
disc.yourwebapps.com/Indices/244066.html
disc.yourwebapps.com/Indices/244067.html
http://sci.med.narkive.com/covV2Qo2/jeffrey-dach-book-announcment-natural-medicine-101
The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.
Link to this Article
Copyright (c) 2024 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given. See Repost Guidelines.
FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.
Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation
Leave a Reply
You must be logged in to post a comment.