top of page

Pros and Cons/ Risks and Side Effects of Hormone Replacement Therapy by Route of administration

Pros and Cons/ Risks and Side Effects of Hormone Replacement Therapy by Route of administration :

Bioidentical hormone replacement therapy (BHRT) is a treatment approach that aims to restore hormone balance in individuals experiencing hormonal imbalances or deficiencies. BHRT can be administered through various routes, each with its own pros and cons. Here's a breakdown of the pros and cons of the commonly used routes of BHRT medication administration:

Oral Administration:

Pros: Convenient and easy to take.Familiar method for most patients.May be more cost-effective compared to other routes.

Cons:Hormone metabolism in the liver can result in variable hormone levels, increased risk of liver-related side effects, limited dosing flexibility as the liver can affect hormone potency (this is why we do not offer certain hormones this route such as testosterone because it can cause liver damage). 

Topical Administration (Creams, Gels, Patches):

Pros:Absorbed directly through the skin, bypassing the liver and reducing liver-related side effects.Steady and controlled hormone delivery over a specific duration (if applied correctly and consistently). Dosage can often be adjusted easily to suit individual needs.

Cons:Application can be messy or inconvenient.Skin sensitivity or allergic reactions to the delivery system may occur.Absorption rates can vary between individuals, affecting hormone levels. There have been some reports of transferring the medication/hormone to small children, would recommend caution in those who are rubbing up against others in where this can become problematic. 

In effort of avoiding iatrogenic transfer to others,  we recommend avoiding contact with others by allowing 4 hours before contact or exposure once applying. Applying at 7AM and 7PM is best. Wash hands to avoid transference to others and cover application sites.

Sublingual Administration:

Pros:Hormones are absorbed directly into the bloodstream through the mucous membranes under the tongue.Bypasses the liver, reducing the risk of liver-related side effects.

Allows for more rapid absorption and potentially quicker symptom relief.

Cons:Taste or texture of sublingual medications may be unpleasant for some individuals.

May require frequent dosing due to faster absorption rates.Hormone levels can still fluctuate significantly if labs are not drawn accurately or if the compliance has been inconsistent. 

Pellet Implants:

Pros: Provides a long-lasting and steady release of hormones over several months.Reduces the need for frequent dosing or application.Mimics the body's natural hormone secretion patterns more closely.

Cons: Requires a minor surgical procedure for implantation.Potential for infection or other complications associated with the insertion site.Difficult to adjust dosages once the pellets are implanted.


Pros: Consistent/reliable dosing if compliance and labs are done correctly 

Cons:Can be painful, usually needs twice a week injections to avoid roller-coaster effects, testosterone injections can adversely affect HDL/cholesterol 

It's important to note that the pros and cons of BHRT routes of administration may vary depending on individual circumstances and preferences. Our providers who specialize in hormone therapy can help determine the most suitable route for your specific needs, taking into account factors such as hormone levels, medical history, lifestyle, and personal preferences.

Benefits and Potential Risks/ Side Effects of Individual Hormones/ Additional Medications that may be used in therapy include but are not limited to:


  • A prescription hormone given by subdermal pellet, injection, troche, or transdermal cream.

  • FDA approved to treat symptoms of andropause/diagnosis of hypogonadism when 2 separate tests show levels < 300 ng/dl.**May qualify through insurance for treatment ***If this is the case, we recommend additional testing to further diagnose if deficiency is secondary to hypothalamic failure (seen in conditions such as a pituitary adenoma) vs. primary testicular failure. 

  • Not FDA approved as an “anti-aging”- However, over 90% of prescriptions are written for off-label use studies that demonstrate a decrease in morbidity and mortality over time.

Potential benefits include increased libido and clitoral sensitivity, energy strength and endurance,  decreased hot flashes, increase in muscle mass which maintains metabolism and decrease in visceral fat, improved insulin sensitivity, improved lipid panel which can lead to a decrease in cardiovascular disease, decreased risk of dementia, decreased bone loss,decrease in wrinkles, fat deposition, and cellulite, increases collagen and skin thickness, leading to improved skin texture, improved cognition and memory. Breast cancer protection

Some women may require high doses to see benefits, while others need lower doses.  

Use the lab tests to demonstrate improvement above baseline and for no other reason. 

Most studies demonstrate very supraphysiologic levels to be therapeutic, and there is no standard or guide on how high one should go which makes testing nebulous.

Risks of testosterone replacement may include, but are not limited to: an increase in red blood cells (erythrocytosis/secondary polycythemia; which we will typically send for therapeutic phlebotomy if a hematocrit increases above 54%/or at customized provider threshold) reduced insulin requirements in insulin-dependent diabetics, increased estradiol levels, edema (fluid retention) and feeding hormone responsive cancers.

Male Specific:There is a risk of infertility/sterility in males as it can cause a decrease in sperm production and a decrease in testicle size. While there are ways to mitigate this risk, we do not recommend any man who wants to preserve his fertility to initiate hormone optimization. 

I understand that with any testosterone treatment, that I will produce less testosterone from my testicles and if I stop replacement, I may experience a temporary decrease in my testosterone production. I understand that compliance with additional pharmaceuticals as prescribed is imperative to ensure best success for my body to eventually begin reproduction but understand that this will likely fall back to pre-treatment levels and the symptoms I endured pre-treatment will likely return. I understand that I should have at least one annual PSA to ensure I am not worsening an unknown prostate cancer (1 in 7 men will get prostate cancer regardless of testosterone therapy but testosterone therapy can feed/grow hormone responsive cancers.)

Female Specific: Premenopausal females MUST use birth control.Testosterone is a known teratogenic and should not be used in pregnant females or those planning to become pregnant as it can also cause virilization of a fetus (masculinize a female fetus)

Side effects may include, but are not limited to: enlarged clitoris, hormonal acne or back acne, temporary water retention, acne,irritability, hirsutism (facial hair)  These are mostly dose related and usually resolve with reduction in dose or addition of spironolactone; however, it can take up to 6 months for hirsutism and acne to resolve. Insulin resistance/ PCOS can also cause acne/hirsutism  as they often cause low SHBG which can cause or worsen hirsutism. If this is the case, treating the insulin resistance to raise SHBG will also help improve these symptoms. It can also cause “PMS” type symptoms such as mastalgia (nipple tenderness) which can be improved with medications such as an aromatase inhibitor (anastrozole) or nutraceuticals to decrease estrogen levels such as DIM or by decreasing the dose. 

Natural testosterone does not equal synthetic testosterone. Synthetics raise cholesterol and lowers HDL, as opposed to natural testosterone which lowers cholesterol and raises HDL (opposite of synthetics). We will monitor lipid levels annually/as seen appropriate by the provider to ensure that if synthetic testosterone is utilized, this is being monitored and treated accordingly. 

Some patients may be on additional medications to help improvement in other hormone related issues such as hair loss or benign prostate hypertrophy; medications that are commonly used to treat these conditions such as finasteride or dutasteride can affect important lab results. If I am on any additional medications, I will ensure that these are fully disclosed to ensure best and safest care. 


Active prostate cancer; men who do not want to risk their fertility should not use testosterone.

Men who want to preserve their fertility should consider banking sperm prior to treatment or consider HCG or Clomid which does not affect fertility; these should also be used in conjunction with testosterone to help endogenous production not be affected by the negative feedback system. 

Estradiol: A prescription hormone, given by subdermal pellet, oral tablet, cream, patch, or troche.


For use in menopause only; not for use in premenopausal women. Menopause is defined as an FSH >50 or absence of a period for longer than 12 months. 

Potential benefits includes increased libido, sense of well-being, increased energy, decreased hot flashes/night sweats, temperature dysregulation, decreased vaginal dryness,vaginal atrophy, urinary incontinence, UTI’s, decreased risk of  cardiovascular disease and stroke when started in the first years of menopause, decreased risk of dementia, decreased bone loss/osteoporosis, improved cognition and memory/alzheimer's disease, help with sleep issues, helps with urinary incontinence.Contraindications:

History of breast cancer; if history of blood clots, should use transdermal route

Side effects may include, but are not limited to: increased body fat, bloating, breast swelling/tenderness, fluid retention and uterine bleeding.These side effects can typically be resolved with dose adjustments/balancing of the three main hormones. Progesterone will help decrease high estradiol levels. It is not uncommon for postmenopausal women to have a period after starting BHRT, however, if persistent bleeding or spotting may warrant additional work up; including labs, a vaginal ultrasound, and possibly an OB-GYN referral if any of the results come back abnormal or if the bleeding persists despite hormone balancing. 

Progesterone:  A prescription hormone, given orally or by transdermal cream.

Potential benefits include protection from estrogen's effect on the uterus and breast thereby reducing risk of endometrial (uterine) and breast cancer, treatment of irregular menstruation/PMS,, improved sleep quality, and improved anxiety and can improve post partum depression when used at high doses.Reduces fluid retention, bloating, headache, bleeding, and fibroids.Can  decreases headache, cyclical migraines, and bloating associated with menstruation when used in high doses.

Side effects can include; drowsiness with oral form due to first pass effect (ODT form does not cause drowsiness),; therefore, only take oral at bedtime, one hour before sleep. Breast or nipple tenderness with oral form, switching to a sublingual form will resolve. Do not recommend a transdermal approach as monitoring is too unreliable and benefits will likely never be obtained due this way as it is not very effective. 

Dehydroepiandrosterone - DHEA:  DHEA is classified as a dietary supplement given orally or by transdermal cream.DHEA is a hormone secreted by the adrenal glands. This hormone is a precursor to other sex hormones. In addition to having its own hormone effect, it results in a shift to an anabolic or protein building state.

Potential Benefits: It reduces cardiovascular risk by increasing lipolysis or breakdown of fat. It also may improve adrenal fatigue/exhaustion, restores sexual vitality to improve erectile dysfunction, improves mood, decreases cholesterol and body fat which may help decrease cardiovascular risks. Recent studies point to DHEA as an anti-stress hormone, reversing the effects of stress on the immune system by acting on T cells.

Contraindications : avoid in patients with a history of hormone responsive cancers.

Side effects of DHEA replacement are generally dose related and may include but are not limited to: acne or oily skin, hair growth on the face, arms or legs, acne in women, prostate enlargement in men, male pattern baldness, decreased HDL cholesterol, fatigue, mood changes,  weight gain and insomnia. If any side effects there is no push to continue for patients under age 40. 


Pharmacological Category: 

Antihypertensive; Diuretic, Potassium Sparing; Mineralocorticoid (Aldosterone) Receptor Antagonist

Use: FDA Labeled Indications

-Ascites due to cirrhosis: Management of edema in cirrhosis of the liver unresponsive to fluid and sodium restriction.

-Heart failure with reduced ejection fraction: To increase survival, manage edema, and reduce need for hospitalization in patients with heart failure with reduced ejection fraction and New York -Heart Association class III to IV symptoms; usually administered in conjunction with other heart failure therapies.

-Hypertension, chronic: Management of hypertension unresponsive to other therapies.

-Primary hyperaldosteronism 

Use: Off-Label:

Acne vulgaris, females, moderate to severe; Hair loss, female pattern; Heart failure with preserved ejection fraction; Hirsutism, females; Hormone therapy for transgender females (assigned male at birth); Post myocardial infarction, complicated by reduced ejection fraction


Spironolactone has some unique properties that make it useful for specific conditions.

One of the main reasons doctors prescribe spironolactone is to help regulate the balance of fluids and electrolytes in your body. It works by reducing the amount of water and salt reabsorbed by the kidneys, which can help you get rid of excess fluid and prevent your body from retaining too much water.

Spironolactone is commonly used to treat conditions such as high blood pressure, edema (swelling caused by excess fluid buildup), and certain hormonal imbalances. In particular, it is known for its ability to block the effects of a hormone called aldosterone, which can cause your body to retain too much salt and water.

For women, spironolactone can also be prescribed to help manage conditions such as polycystic ovary syndrome (PCOS), hirsutism (facial hair) and acne. In these cases, the medication can help reduce the production of androgens, which are hormones that can contribute to acne breakouts and other symptoms of PCOS.


It's important to note that spironolactone may take some time to show its full effects (up to 6 months at times for androgen improvement) ! Your doctor will typically start you on a low dose and adjust it as needed to find the right balance for your condition. It's crucial to follow your doctor's instructions carefully and take the medication as prescribed.

Potential side effects/risks. increased urination, dizziness, stomach upset, and changes in electrolyte levels if dehydrated. It is essential to let your doctor know about any other medications or supplements you are taking, as spironolactone can interact with certain drugs, including some blood pressure medications and potassium supplements. It is also essential that you stop taking this medication if you feel dehydrated and notify your provider if this occurs for further instruction. 

bottom of page