From a clinical standpoint, the two major problems women face in terms of sexual activity are mainly a low sex drive and pain during sexual intercourse.

The use of both oral and topical intravaginal hormone replacement therapy solves the problem quickly and almost completely. Testosterone has been shown to improve a woman’s sex life in all areas (sexual desire, ease of achieving orgasm…), and there is growing confidence in its usefulness and, above all, its safety.

Dr. Francisco Martínez Peñalver – Neolife Medical Team

Dyspareunia usually occurs in menopausal women, and one in three women between the ages of 40 and 64 suffer from HSDD

Culturally speaking, one of the taboos we have overcome in recent years, for the most part, is the one related to a woman’s sex life. The question “what is your sex life like?” made both doctor and patient feel uncomfortable despite the sheer amount of information that could potentially be gleaned from it.

One of the most significant changes of the 21st century is that when a doctor tries to gather information for a patient’s medical history, this barrier seems to have been knocked down, and now the doctor is willing to ask, and the patient is willing to answer. The training doctors receive has, to a great extent, changed in relation to ways of gathering information for the anamnesis, but patients also have increasingly come to understand that if they don’t report a problem, the doctor will hardly be able to help.

From a clinical standpoint, the two major problems women face in terms of sexual activity are mainly a low sex drive (hypoactive sexual desire disorder or HSDD) and pain during sexual intercourse (also called dyspareunia) (1).

Dyspareunia usually occurs in menopausal women as a result of the atrophy of the genitourinary system caused by the end of the supply of female sex hormones it used to receive. This atrophy is linked to the onset of vaginal dryness for the same reason (2). There is a non-topical non-estrogenic solution that alleviates the problem, at least partially, but the use of both oral and topical intravaginal Hormone Replacement Therapy solves the problem quickly and almost completely. New techniques with CO₂ laser have recently been developed, where the laser is applied to the external labia in order to increase collagen and, therefore, increase the thickness of the vaginal epithelium; however, only observational studies have been conducted at the moment, and there are no clinical trials that guarantee the results obtained.

In the case of HSDD, extensive epidemiological studies reveal that 1 in 3 women between the ages of 40 and 64 suffer from this disorder, with a prevalence that increases with age due to not only biological, but also psychological and cultural causes. To remedy this problem, there are two pharmacological solutions. First, there is a drug called flibanserin, wrongly labeled “the female viagra”, which lowers serotonin levels and increases other substances linked to sexual desire such as dopamine and norepinephrine (3). It should be taken with caution; it shouldn’t be mixed with alcohol. The results of the research conducted report an increase in frequency to twice the number of sexual encounters a month.

The other option is testosterone (4), which, starting in the mid 30s, has gradually decreased its levels in women, with a more pronounced drop once a woman hits menopause. Testosterone has shown to improve a woman’s sex life in all areas (sexual desire, ease of achieving orgasm, etc.), and there is growing confidence in its usefulness and, above all, its safety.

Very promising products are currently being developed to address these problems, for example, one that combines the beneficial properties of testosterone with buspirone, a drug used to treat anxiety that will override the natural opposition of the brain to sexual intercourse. Another product currently being developed is bremelanotide, which acts at the brain level on the neural pathways that condition sexual response in women. It produces the same effect as flibanserin and decreases serotonin levels and increases dopamine and norepinephrine levels, with very few side effects, namely nausea and dizziness.

At Neolife, we believe that one of the most important aspects in a patient’s life is her sexual health. That is why one of the benefits our patients obtain from the Age Management Plan is an obvious improvement in their sex life.

BIBLIOGRAPHY

(1) Clayton AH et al. Evaluation and management of hypoactive sexual desire disorder. Sex Med 2018;6:59-74.

(2) Faubion SS et al. Genitourinary syndrome of menopause: management strategies for the clinician. Mayo Clin Proc. 2017;92:1842-1849.

(3) Holt H et al. Flibanserin for hypoactive sexual desire disorder in premenopausal women. Am Fam Physician. 2016;93:826-828.

(4) Davis SR et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med. 2008;359:2005-2017.

Erectile dysfunction is defined as the persistent inability to achieve or maintain an erection that allows for satisfactory sexual intercourse.

Having good testosterone levels is critical to having satisfactory erections, but there are many more factors involved. It can happen for vascular, neurogenic, anatomical, hormonal, drug-induced or psychogenic reasons. In many cases more than one cause is to blame.

Dr. Alfonso Galán González – Neolife Medical Team

Epidemiological data reveal a high incidence and prevalence of erectile dysfunction globally.

Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection that allows for satisfactory sexual intercourse.

Epidemiological data reveal a high incidence and prevalence of erectile dysfunction globally. The Massachusetts Male Aging Study (MMAS) indicates a prevalence of 52% (to varying degrees) among men between the ages of 40 and 70 in the New England region. In a German study on men between the ages of 30 and 80, however, the prevalence was 19.2%, with a very significant increase with age from 2.3% to 53.4%. A Dutch study of men in consultation for erectile dysfunction observed that 1 in 4 were under the age of 40, and half of them reported severe erectile dysfunction.

To better understand the causes that can lead to erectile dysfunction, we’re going to look at what phenomena must occur for a man to have a satisfactory erection.

An erection occurs when 2 tubular structures, the corpora cavernosa that run all the way through the penis and the corpus spongiosum containing the urethra, fill with blood. This can occur due to a series of physiological stimuli such as arousal and sexual stimulation, processes with a strong hormonal influence, especially testosterone.

In the presence of mechanical stimulation, the erection is initiated by the parasympathetic nervous system (a division of the autonomic, unconscious or voluntary, nervous system). These parasympathetic nerve branches range from the sacral plexus to the arteries that reach the erectile tissue. When stimulated, acetylcholine is secreted, which causes the release of nitric oxide, a vasodilator agent. Thus the arteries dilate and fill the corpora cavernosa with blood.

The next step is preventing that blood from receding. The ischiocavernosus and bulbous muscles compress the veins, preventing the blood from being drained. After ejaculation or the cessation of stimulation, parasympathetic stimulation disappears and the blood leaves the corpora cavernosa through the venous system.

The cerebral cortex, i.e. our superior, more advanced brain functions, can initiate erection in the absence of stimulation in response to visual stimuli, olfactory stimuli, imagination, etc. They operate through erection centers in the sacral and lumbar regions of the spinal cord. Moreover, the cerebral cortex can suppress erection, even in the presence of mechanical stimulation, as can other environmental, psychological or emotional factors.

Erection can also occur spontaneously at night, in a process that is believed to be mediated by the brainstem during the REM sleep phase and is thought to be a form of “maintaining” the proper health of our erections. The presence or not of these nocturnal erections has diagnostic value.

In view of this, we can understand the large number of mechanisms required for an erection to occur and the large number of steps at which it can fail. Erectile dysfunction can occur for vascular, neurogenic, anatomical, hormonal, drug-induced or psychogenic reasons. In many cases more than one cause is to blame.

1. Vascular:
   • Habits (smoking).
   • Sedentary lifestyle and lack of exercise.
   • Obesity.
   • Cardiovascular disease (high blood pressure, coronary heart disease, peripheral artery disease, etc.).
   • Diabetes, dyslipidemia, metabolic syndrome, hyperhomocysteinemia, etc.
   • Pelvic surgery sequelae (prostatectomy or radiation therapy).
2. Neurogenic:
   • Main causes:
     • Degenerative diseases (multiple sclerosis, Parkinson’s, etc.).
     • Spinal diseases or trauma.
     • Stroke.
     • CNS tumors.
   • Peripheral causes:
     • Diabetes.
     • Kidney failure, liver failure.
     • Polyneuropathy.
     • Pelvic surgery with nerve damage.
     • Urethral surgery.
3. Anatomical or structural:
   • Hypospadias, epispadias.
   • Peyronie’s disease.
   • Penile cancer or other external genital tumors.
4. Hormonal:
   • Diabetes mellitus; metabolic syndrome.
   • Hypogonadism.
   • Hyperprolactinemia.
   • Hyper and hypothyroidism.
   • Hyper and hypocortisolism.
   • Multiple endocrine disorders.
5. Mixed mechanisms:
   • Chronic illness.
   • Psoriasis, gouty arthropathy, ankylosing spondylitis, hepatic steatosis, chronic periodontitis, glaucoma, inflammatory bowel disease, etc.
   • Iatrogenesis.
6. Drug side effects:
   • Antihypertensive drugs (thiazides, beta blockers, etc.).
   • Antidepressants.
   • Antipsychotics.
   • Antiandrogens (GNRH analogues, 5-alpha-reductase inhibitors).
   • Drug abuse (alcohol, heroin, cocaine, marijuana, methadone, synthetic drugs, anabolic steroids, etc.).
7. Psychogenic:
   • Generalized type (lack of arousal or sexual intimacy disorders).
   • Situational type (related to the relationship, with execution or with stress).
   • Trauma.
   • Penis fracture.
   • Pelvic fractures (1).

Diagnosing the particular cause of erectile dysfunction requires careful medical evaluation, with detailed anamnesis on habits, history, illnesses, drug taking, specific sexual questionnaire, psychiatric or emotional symptoms, etc. A physical examination of the area checking for deformities, prostate exam, signs of hormonal, vascular or neurological disease. A complete analytical study with blood count, hormone levels (free testosterone, dehydroepiandrosterone, estradiol, prolactin, etc.) and metabolic parameters and cardiovascular risk.

The study can be completed with more specific tests such as the doppler ultrasound of the penis with provocation tests or nocturnal tumescence testing. This test is important because if the patient is able to have erections at night we can assume that the vascular and neurological mechanisms are working and the cause is more likely psychogenic.

What can be done?

Treatment will ideally be aimed at correcting the suspected cause of erectile dysfunction. It is based on hygienic-dietary measures and modification of habits, pharmacological measures, physical therapy and finally surgical therapies to restore flow or implantation of prostheses.

• Modification of harmful lifestyle habits is fundamental and should be considered prior to other therapeutic approaches and treatments. These include:
  • Quitting smoking.
  • Drinking in moderation.
  • Get a good night’s sleep.
  • Good dietary habits. Monitoring the intake of sugars and saturated fats and increasing the consumption of vegetables.
  • Performing regular exercise. 30 minutes, 5 times a week. Some studies show benefits from performing pelvic floor exercises (Kegel) (2).
  • Encourage communication and trust with your partner.
• More and more pharmacological measures are becoming available to improve blood flow to the penis such as sildenafil and Tadalafil or Alprostadil.
• Newer treatments such as the use of shock waves to stimulate the creation of new blood vessels and improve flow are yielding very promising results.

And perhaps in a class of its own, straddling the line between lifestyle changes and pharmacology, is the hormone replacement therapy with bioidentical hormone that we have developed at Neolife. This therapy is very helpful and is primarily aimed at achieving adequate physiological levels of DHEA and testosterone. The Massachusetts Male Aging Study looked at the correlation of 17 hormones and erectile dysfunction and found that only DHEA had a negative relationship (i.e. greater dysfunction at lower levels). This led researchers to study its effect on this pathology in detail. Reiter et al. showed improvements in erectile dysfunction, satisfaction during coitus, sexual desire and orgasmic function after 16 weeks of use (3). Meanwhile, treating male hypogonadism by replenishing testosterone levels has been shown in several recent meta-analyses to improve erectile function, sexual desire and orgasmic function (4).

The conclusion that we want to convey here at Neolife is that erectile dysfunction is a multi-factor clinical picture that must be evaluated and treated from multiple axes, hormonal therapy being a very important one, but still just one of them.

BIBLIOGRAPHY

(1) https://uroweb.org/guideline/male-sexual-dysfunction/#3

(2) Dorey, G. , Speakman, M. J., Feneley, R. C., Swinkels, A. and Dunn, C. D. (2005), Pelvic floor exercises for erectile dysfunction. BJU International, 96: 595-597

(3) Reiter WJ, Pycha A, Schatzl G, Pokorny A, Gruber DM, Huber JC, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology 1999;53:590–4.

(4) Corona G, Rastrelli G, Morgentaler A, Sforza A, Mannucci E, Maggi M. Meta-analysis of Results of Testosterone Therapy on Sexual Function Based on International Index of Erectile Function Scores. Eur Urol. 2017 Dec;72(6):1000-1011.

Testosterone has always been seen as a double-edged sword: on the one hand, it has significant benefits for the body and, on the other hand, it is seen as a risk factor for the onset of hormone-dependent tumors such as prostate cancer.

A recent study by Spanish researchers, who presented their work at the last European urology congress, was published in which they not only reject the notion that testosterone causes prostate cancer, but also suggest that, in fact, having levels within normal range improved the prognosis of patients already diagnosed with the disease and who had undergone a radical prostatectomy.

Dr. Moisés De Vicente – Neolife Medical Team

Little by little, testosterone is breaking free from its bad reputation.

Testosterone has always been seen as a double-edged sword: on the one hand, it has significant benefits for the body and, on the other hand, it is seen as a risk factor for the onset of hormone-dependent tumors such as prostate cancer.

Testosterone is an essential hormone for the proper functioning of our bodies. However, over the years, there is a decline in production in both men and women, which is often accompanied by symptoms such as lack of vitality and decreased sexual desire. However, in addition to these symptoms, testosterone directly influences the regulation of lipid metabolism, carbohydrate metabolism and is capable of modulating the functionality of different cells and tissues such as the endothelial tissue that covers our arteries, muscle, bone tissue, visceral fat, and hematopoietic tissue (1).

Most of these actions are performed by stimulating an androgenic receptor and activating growth factors, which are responsible for stimulating cellular metabolism. Logically, the lack of activity among these receptors due to the progressive decline in testosterone production that occurs over the years results progressively in the onset of sexual dysfunction, loss of muscle and bone mass and the increase of visceral fat.

In short, the lack of testosterone results in multiple deleterious processes for our body. This could be corrected by administering the hormone of which we have a deficiency. However, the fear that the onset of a tumor might be precipitated means that it is not used in many cases where it is clearly necessary. That’s the downside.

However, it appears there may be an unexpected upside, or at least one that wasn’t fully understood by our colleagues who performed hormonal studies in the past. A recent study by Spanish researchers, who presented their work at the last European urology congress (2), was published in which they not only reject the notion that testosterone causes prostate cancer, but also suggest that, in fact, having levels within normal range improved the prognosis of patients already diagnosed with the disease and who had undergone a radical prostatectomy.

The study looked at 824 patients with this condition. 152 of them in whom low levels of testosterone were observed prior to surgery were treated with transdermal testosterone. What they later found was that this group of patients had a lower rate of biochemical recurrence (PSA levels) after one year of surgery compared to those who did not receive the hormone supplement. It was estimated that more than half (up to 53%) benefited from this treatment. Moreover, testosterone use was associated with a longer period before the recurrence or progression of the tumor. Specifically, patients who received testosterone took up to one and a half years longer to develop recurrences compared to those who did not receive testosterone.

Upon reviewing the results, researchers were surprised to find that the patients with more advanced tumors were those with lower levels of testosterone at the time of diagnosis, whereas those who had levels within normal range at the time of diagnosis had less aggressive tumors.

Until now, the adjuvant treatment for this type of tumor had been chemical castration through the use of anti-androgenic drugs. However, this study is turning all the guidelines upside down by presenting a therapy that is the complete opposite of what had been done so far.

Let’s put ourselves in the shoes of one of these patients. Thanks to this finding, I’ll be able to begin treatment with testosterone. Not only do I recover my sexual desire, my vitality and my mood after undergoing such a disruptive event as a tumor diagnosis and the invasive surgery performed on me, but the “cost” of regaining all of those vital functions for the physical and mental well-being of my body is none other than an improvement in my tumor’s prognosis!

Clearly, more studies are needed in this regard that include more patients at different tumor stages, etc. But the groundwork has been laid. It is very likely that, in the near future, treatment guidelines will change, and ensuring that adequate levels of testosterone are achieved in these patients will be encouraged to improve their survival rates. And with this comes an improvement in their quality of life.

So it seems that little by little testosterone is breaking free from its bad reputation, even among subjects who, according to the “old medical belief”, ought to fear it the most.

In healthy patients, treatment with testosterone is safe. There are no articles that suggest its use is related to the appearance of tumors. And after seeing how prostate cancer patients are “protected”, it seems unlikely that they will be published

At Neolife we consider treatment with testosterone fundamental in patients with androgenic deficit syndrome. By using it we are able to prevent diseases that are clearly related to its absence and, moreover, we alleviate symptoms produced by low levels of the same. We’re certainly on the right path.

BIBLIOGRAPHY

(1) Araujo AB, Dixon JM, Suarez EA et al. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96: 3007–3019

(2) European Association of Urology (EAU) 2019 Congress: Abstract 646. Presented March 17, 2019.

Bioidentical testosterone therapy, at the right doses, is completely safe and allows for a correct hormonal restoration. Nevertheless, myths and rumours still circulate despite lacking any scientific evidence.

Some of the misconceptions that abound in the collective imagination are: that testosterone is a “male” hormone; that its only role in women is for sexual desire and libido; that replacement therapy makes women more masculine; that it gives you a deeper (more manly) voice; that it causes hair loss; that it can have adverse side-effects on your cardiovascular system; that it causes aggression; or that it can increase the risk of breast cancer.

Dr. Iván Moreno – Neolife Medical Team

Many of these myths that create such a bad reputation for hormones are in fact extrapolations of the adverse effects seen from taking very high doses of anabolics, which have nothing to do with bioidentical testosterone.

Testosterone therapy is being increasingly used to alleviate symptoms of hormonal deficiency in pre and postmenopausal women.

Although numerous scientific studies show the safety and success of this treatment, rumours and myths have been created, which by sheer force of repetition seem to hold more “influence” despite lacking any supporting medical evidence.

Many of these myths are extrapolations of the adverse effects seen from taking very high doses of anabolics (testosterone derivatives) for other purposes (such as bodybuilding, doping, etc.).

In this article, we refer solely to therapy with bioidentical testosterone (which is identical to a human testosterone molecule) and only at replacement doses which aim to replenish the physiological levels we already had in our youth; this is the standard that governs a correct hormone restoration, which we employ here at Neolife.

Myth 1: Testosterone is a “male” hormone.

While it is true that men have higher levels of testosterone, the most abundant sex hormone present in a women’s body is also testosterone. Oestrogen (typically referred to as the “female” hormone), although present throughout a women’s life, is found in concentrations 10 times lower than that of testosterone. Testosterone, in balance with lower doses of oestradiol, is equally important for both sexes.

Fact: testosterone is the most abundant and biologically active hormone in women.

Myth 2: The only role of testosterone in women is for sexual desire and libido.

Another misconception, given that testosterone receptors are found in practically all tissues of a women’s body. Testosterone and its precursors decrease with age, and pre and postmenopausal women may experience symptoms of androgen deficiency such as: mood disorders, lack of well-being, fatigue, loss of bone density and muscle mass, mental dullness, memory disorders, hot flushes, joint discomfort, and sexual dysfunction etc.

Fact: testosterone is essential to a woman’s physical and mental health.

Myth 3: Testosterone treatment makes women more masculine.

Restoring a woman’s ideal hormone levels (to that which we had between the ages of 18-25 years old) far from making you more masculine, can in fact make you more feminine. Treatment should not be confused with the high supra-pharmacological doses which are administered to patients requiring more drastic changes due to gender issues; in which case, symptoms are still reversible by merely reducing the dosage.

Fact: excluding supra-pharmacological doses, testosterone has no masculinizing effects on women.

Myth 4: Testosterone will make your voice deeper (more masculine).

Hoarseness of voice can affect us at different times due to inflammation or infection of the throat, but is always reversible. There is no procedure whereby testosterone could produce such a phenomenon; even in cases of high doses of other androgens, there is no clear evidence of producing a deeper voice or any irreversible changes to the vocal chords.

Fact: there is no evidence that testosterone changes your voice.

Myth 5: Testosterone causes hair loss.

Hair loss is a complex and multifactorial process which is also genetically determined. “Androgenic” alopecia refers to the similar type of pattern baldness commonly found in men, not referring to the cause, but rather to the defined pattern. In any case, it is dihydrotestosterone (DHT), and not testosterone, which is involved. Obesity and insulin resistance, as well as alcohol, a sedentary lifestyle and some medications, can increase the conversion of testosterone to DHT and oestradiol in the hair follicle.

Approximately one third of women experience brittle hair and hair loss with age, which often coincides with a decrease in testosterone levels. However, there are studies in which hair regrowth has been achieved due to subcutaneous testosterone implants in such women.

Fact: testosterone does not cause hair loss; in fact, in some cases it can improve hair regrowth.

Myth 6: Testosterone has adverse effects at a cardiovascular level.

Unlike synthetic anabolics, there is no evidence that testosterone has any adverse effect at a cardiovascular level. In fact, its replacement has a beneficial effect on the metabolism of glucose and lipids, as well as on the maintenance of “lean mass” in both men and women’s bodies.

The most complete meta-analysis ³ carried out on this topic shows that there is no greater cardiovascular risk with testosterone replacement therapy; in fact, a lower occurrence of cardiovascular disease has been demonstrated in some groups (those presenting a higher cardiometabolic risk).

Fact: there is substantial evidence supporting the cardiovascular safety of testosterone, which even indicates a likely protective effect.

Myth 7: Testosterone damages the liver and can cause “clotting” (venous thromboembolic disease).

This is an “imported” rumour from the world of anabolic (synthetic androgens) over-use, which when taken orally in high doses, can in effect, cause liver damage. The truth is that parenteral testosterone (gels, skin patches or subcutaneous implants) avoids that first step through the liver and thus has no adverse effects (i.e. there is no increase in transaminase enzymes nor any alteration to the factors that affect blood clotting). There is therefore no relationship between testosterone administered in this way and the occurrence of blood clots (thrombosis, embolism), unlike synthetic steroids, or oestrogens taken without progesterone and progestins.

Fact: non-oral testosterone does not damage the liver or increase blood clotting.

Myth 8: Testosterone causes aggression.

Although the use of anabolics at high doses can cause aggression and attacks of “rage” (hence the rumour), this does not happen with testosterone. Even with supra-pharmacological doses of intramuscular testosterone, there has been no clear onset of aggression.

As has been previously mentioned, in cases of obesity, alcohol consumption, or a marked sedentary lifestyle, the conversion rate of testosterone to oestradiol can be seen to increase. The effects of excess oestrogen (oestradiol and its derivatives) however, have been associated with irritability and aggression in other species. In fact, in women presenting symptoms of androgen deficiency, treatment with testosterone has been shown to improve anxiety and irritability in more than 90% of cases².

Fact: testosterone therapy is not linked to aggression; even in women suffering from testosterone deficiency, therapy improves anxiety and irritability.

Myth 9: Testosterone may increase the risk of breast cancer.

Since 1937, it has been known that the development of breast cancer is usually dependent on oestrogen. Testosterone, however, could play a possible role in slowing down the growth of breast tissue, and may even be a treatment for breast cancer.

In recent studies, in which testosterone was administered together with an aromatase inhibitor (preventing any conversion into oestrogen), they found the tumour to reduce or even disappear⁵.

Fact: testosterone does not increase chances of breast cancer; in fact, it could help to prevent it.

Myth 10: the safety of testosterone use in women has not been tested.

Data of treatment at very high doses in transgender patients has existed for more than 40 years, and has shown this treatment to be safe. Any side-effects have been the consequence of oral intake (which is no longer used) or due to the conversion to oestradiol (which is rarely a problem at the doses used for bioidentical hormone replacement).

Fact: the safety of non-oral testosterone use has been well established in women for cases of very long-term treatments.

BIBLIOGRAPHY

(1) Glaser, R., & Dimitrakakis, C. (2013). Testosterone therapy in women: myths and misconceptions. Maturitas, 74(3), 230–234.

(2) Glaser R, York AE, Dimitrakakis C. Beneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS). Maturitas 2011; 68: 355–61.

(3) Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late onset hypogonadism: systematic review and meta- analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab 2013; 27: 557-579.

(4) Hackett, G., Kirby, M., Edwards, D., Jones, T. H., Wylie, K., Ossei-Gerning, N., et al. (2017). British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. The Journal of Sexual Medicine, 14(12), 1504–1523.

(5) Glaser, R., & Dimitrakakis, C. 2015. Testosterone and breast cancer prevention. Maturitas, 82(3), 291–295.