Please read this form in its entirety. It contains important information to assist you in deciding whether or not to receive Bio-identical Hormone Replacement Therapy (Estrogen, Progesterone, Testosterone). The purpose of this informed consent form is to give you written information regarding the potential risks, benefits, and alternatives with respect to bioidentical hormone replacement therapy (BHRT) so that you can provide true voluntary informed consent to receive this treatment. This material serves as a supplement to the discussion you have with your medical provider about the treatment. It is important that you fully understand this information, so please read this document thoroughly. If you have any questions regarding BHRT, ask your medical provider.

Background of Bioidentical Hormone Replacement Therapy: You have been diagnosed with a relative or absolute deficiency of estrogen, testosterone, or progesterone or a combination thereof, and your medical provider has determined that you may potentially benefit from supplementation with bioidentical hormones. Your medical provider has recommended treatment with bioidentical hormone replacement therapy (also referred to as BHRT) which consists of Estradiol, Estriol, Progesterone, Dehydroepiandrosterone (DHEA), and Testosterone, which may be given in any variety of combinations, delivery routes, and dosages depending on my own individual requirements.

Bioidentical hormones have the same chemical formula as those produced by human ovaries, adrenal glands, or other tissues. In other words, the molecules are biologically identical or very similar in composition and structure to human hormones. They are not synthetic or derived from animals. The Effecty medical providers only use bioidentical hormones.

There are different types of bioidentical hormone replacement available as well as routes of administration.

· For estrogen replacement therapy, these include oral capsules and sublingual lozenges (troches), transdermal forms (patches, sprays, gels, creams), injections and subdermal pellets (inserted under the skin that release estrogen into the body over time), and for vaginal use, suppositories, creams, and rings are also available.

· Progestogens, compounds that exhibit progestational activity, include the only natural progestogen, called progesterone, and a variety of synthetic progestogens. Bioidentical progesterone is available in oral, sublingual troche and vaginal cream or suppository, and a transdermal form as a cream.

· Testosterone is also available in oral, sublingual troche and transdermal forms (patches, sprays, gels, creams) as well as injections, and subdermal pellets (inserted under the skin). Testosterone is not FDA approved for women and is considered “off-label” use for symptomatic improvement in women.

Hormone replacement therapy is often prescribed to women during perimenopause (the time from first symptoms to up to several years beyond the last period) and menopause (starting one year after the last period) for symptoms of hot flashes, vaginal dryness, loss of libido, depression, irritability or PMS-like symptoms, bone loss and osteoporosis or its prevention, and cardiovascular disease. Hormone replacement therapy is approved by the FDA for four indications: the treatment of hot flashes (vasomotor symptoms), prevention of bone loss, genitourinary symptoms including vulvovaginal atrophy, and premature hypoestrogenism (due to hypogonadism, premature ovarian failure, or premature surgical menopause). Using it for other symptoms or problems is considered “off-label” use; however, there is positive data supporting the use of hormone replacement therapy for other conditions as further noted below.

It is also important that you know there are significant medical differences of opinion regarding the best method(s) to diagnose and treat low hormone levels, whether blood, urine and/or saliva, and the most appropriate way to monitor dosage and therapy. This is especially true when “standard” blood tests are “normal”, meaning that the result is within the normal laboratory reference range for the test. The diagnosis and treatment used may be considered non-conventional, complementary or alternative. Other physicians may disagree with the need for treatment at all, the method of treatment, dosing and/or the methods of monitoring. Furthermore, most of the long-term research on hormone replacement therapy (HRT) has been done on synthetic forms of HRT; unlike bioidentical forms of HRT which have the same chemical structure as the human body’s own hormones, synthetic forms of HRT do not.

The medical providers prescribe BHRT only in appropriate cases and at levels designed to reduce symptoms of low hormone levels and give back quality of life. Nevertheless, in order to reduce uncertainties and potential risk, patients who are prescribed BHRT must agree to have adequate lab testing, imaging, and physical examinations. All patients who are prescribed BHRT are required to have the following:

· Lab testing (blood work and/or salivary testing) initially prior to starting BHRT and then every three months for the first 6-9 months of treatment until your hormone levels have stabilized and then at least every 6 months thereafter to maintain and refill BHRT prescriptions. Paid follow-up visits with your Effecty medical provider will be required to review all lab results.

· BHRT refills may not be issued if the required testing and follow up reviews are not followed as prescribed.

· Patients must have established care with an OBGYN/gynecologist and be up to date with medical screenings for their age and risk profile throughout the duration of BHRT including:

o An annual mammogram or breast ultrasound depending on age and family history

o Monthly self-breast exams and annual clinical breast exam with a licensed health professional, primary care physician, gynecologist; and

o An annual pelvic exam and transvaginal ultrasound with Pap Smear from a licensed healthcare professional, primary care physician or gynecologist every 3 years until age 75 unless otherwise recommended by your gynecologist.

· A copy of all exams must be provided to your medical provider to continue BHRT prescriptions.

Failure to comply with required follow-up appointments and monitoring, including follow-up lab work, will result in termination of therapy.

Due to the individualized nature of BHRT, many of the hormones prescribed will be from compounding pharmacies.

As with all therapies, there are potential benefits, risks, and alternatives to BHRT explained more fully below.

Potential Benefits of Hormone Replacement Therapy -- Estrogen and Progesterone:

According to the 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS), hormone replacement therapy remains the most effective treatment for vasomotor symptoms (hot flashes) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture.

The decreasing levels of estrogen with menopause are associated with increased risk for cardiovascular disease, osteoporosis, colon cancer and Alzheimer’s disease; menopause/aging is associated with urogenital atrophy, skin aging, osteoarthritis, macular degeneration, and cataract formation. Therefore, hormone replacement has the potential to reduce the risks of these events while also improving quality of life symptoms. There are issues and risks that change with aging which include weight gain, normal amount of bone loss, normal amount of cognitive decline, and increased risk of breast cancer.

In addition to reduction in hot flashes, genitourinary syndrome of menopause, and prevention of bone loss and fracture, the medical literature indicates hormone replacement therapy may have the following potential benefits including:

· Estrogen therapy appears to have beneficial effects on skin thickness and elasticity and collagen when given at menopause.

· Hormone replacement therapy offers significant improvement in quality of life for women with severe menopausal symptoms.

· Hormone therapy improves sleep in women with bothersome nighttime vasomotor symptoms by reducing nighttime awakenings.

· Specifically for women with early menopause (age 40-45) and premature ovarian insufficiency or premature menopause (< 40 y.o.), there are multiple health risks associated with the early loss of hormones including persistent vasomotor symptoms, bone loss, vulvovaginal atrophy, mood changes, and increased risk of heart disease, dementia, stroke, Parkinson’s disease, ophthalmic disorders, and overall mortality. The use of hormone replacement therapy in this population can reduce these risks when taken to at least age 51.

· Preclinical studies suggest a possible benefit of estrogen replacement therapy when combined with exercise to prevent the loss of muscle mass (i.e., prevention of sarcopenia), strength, and performance that can come with age.

· Studies have shown that women on hormone replacement therapy have less joint pain and stiffness compared with those on placebo, and even less osteoarthritis.

· Hormone therapy may help attenuate abdominal adipose accumulation and the weight gains that are often associated with the menopause transition.

· Data suggests that menopausal hormone replacement therapy may result in a reduced heart disease risk for women if initiated within the first 10 years of menopause. This is also likely true with respect to risk reduction of Alzheimer’s disease.

· Observational studies suggest a reduced incidence of colorectal cancer with hormone replacement, particularly if initiated early in menopause.

Potential Side Effects and Risks of Hormone Replacement Therapy – Estrogen and Progesterone:

Potential risks of receiving hormone replacement therapy differ depending on the type of hormones prescribed, including combinations of hormones, as well as dose, duration of use, timing of initiation, and the route of administration (oral or transdermal - patches, sprays, gels, creams, injections, and pellets.) Sublingual deliveries are a combination of oral and transdermal; you swallow some and some goes directly into the blood stream under the tongue.

The medical providers individualize hormone replacement therapy for each patient to identify the most appropriate type, dose, formulation, combination, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing BHRT.

More common adverse effects of estrogen and/or progesterone hormone replacement therapy include: nausea, bloating, weight gain, fluid retention, mood swings vaginal bleeding, headaches, and breast tenderness.

Potential risks of hormone replacement therapy initiated in women who are younger than 60 years of age or who are within 10 years of menopause onset include: the rare possible risk of breast cancer with combined estrogen-progestin replacement therapy; endometrial hyperplasia and endometrial cancer if estrogen is unopposed or inadequately opposed (i.e., when estrogen is used without a progestogen or sufficient progestogen); venous thromboembolism (VTE); and biliary issues. Additional risks across ages include myocardial infarction (MI), stroke, and dementia. However, transdermal and pellet forms of estrogen do not have the same risks as oral estrogen, and bioidentical progesterone does not have the same risks as synthetic progestin.

There appear to be safety advantages with the transdermal, injection and pellet forms of estrogen as compared to oral forms, as the transdermal forms bypass the liver. For example, the oral form of estrogen may infrequently cause the formation of clotting factors and other proteins as it goes through the liver, leading to the potential for venous thromboembolism (deep vein thrombosis and pulmonary thromboembolism); transdermal estrogen replacement therapy does not cause the same formation of clotting factors and other proteins. Additionally, oral estrogen replacement therapy is converted into estrone more readily, which does not have the symptom-relieving effect of estradiol, thus rendering the therapy less effective. Moreover, other benefits of the transdermal form may include better stability of blood estradiol levels, reduction of LDL cholesterol and total cholesterol while not elevating triglycerides (as can occur with oral estrogen), and unlike oral estrogen, transdermal estrogen does not increase the production of the inflammation biomarker C-reactive protein by the liver. Cholelithiasis, cholecystitis, and cholecystectomy (gallbladder disease) are known risks with oral estrogen replacement therapy, but not with transdermal administration.

The use of estrogen alone in a woman with a uterus (without adequate progesterone or progestin) increases the risk of vaginal bleeding, endometrial hyperplasia, and endometrial cancer. Therefore, estrogen replacement therapy alone is used primarily for women who have had their uterus removed. When adequate progesterone is combined with estrogen, the risk of endometrial hyperplasia and cancer is not higher than in women who take no estrogen/progestogen.

Breast Cancer: There is now general agreement, after re-analysis of the 2002 Women’s Health Initiative (WHI) data, that there is no increased risk of breast cancer for women under age 60 who take systemic estrogen and progestins for less than 5.6 years, although the slight increase in risk begins somewhere between year 3 and 4. Whether systemic estrogen replacement alone is a risk factor for breast cancer after long term use is still unclear although the predominant and best research shows that it is not. Estrogen replacement therapy is not generally advised for breast cancer survivors; however, low-dose vaginal estrogen replacement therapy is an option for women with genitourinary syndrome of menopause. Synthetic progestogens have been shown to increase the risk of breast cancer by inducing abnormal cell proliferation. However, some observational studies suggest that breast cancer risk is lower with bioidentical micronized progesterone in oral form along with the estrogen. As noted, the Effecty medical providers use bioidentical oral progesterone unless not tolerated or not acceptable to the patient.

Bioidentical vs. Synthetic and Animal-Derived HRT: One review evaluated studies comparing bioidentical hormones including estradiol, estriol, and progesterone to non-bioidentical (synthetic and animal-derived) hormone replacement therapy. The author of this study concluded that bioidentical hormones were more effective and associated with lower risks of breast cancer and cardiovascular disease than synthetic or animal-derived versions.

Comparing the Risks and Benefits:

· According to NAMS, for women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome vasomotor symptoms and for those at elevated risk for bone loss or fracture.

· According to NAMS, for women who initiate hormone replacement more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

· Hormone therapy does not need to be routinely discontinued in women aged older than 60 or 65 years and can be considered for continuation beyond age 65 years for persistent vasomotor symptoms, quality of life issues, or prevention of osteoporosis after appropriate evaluation and weighing of risks and benefits. Annual reevaluation, including reviewing comorbidities and periodic trials of lowering or discontinuing hormone replacement or changing to potentially safer low-dose transdermal routes, should be considered.

· Low-dose vaginal estrogen preparations are effective and generally safe for the treatment of vulvovaginal atrophy, with minimal systemic absorption, and preferred over systemic therapies. These products do not increase the risk of any cancer or any of the above-mentioned other risks.

Testosterone Replacement Therapy in Women:

· Potential benefits of testosterone therapy in women: There is promising evidence that testosterone replacement therapy can have several benefits for women such as: decreased risk of heart attack and stroke, decreased risk of obesity, increase in bone mineral density, possible improvement in cognition, increase in sexual arousal and increased energy and mood. Other research has shown that testosterone supplementation showed no increase in adverse cardiovascular events as long as testosterone levels remained with normal levels. Testosterone replacement at normal physiological ranges appears safe.

· Potential side effects and risks of testosterone therapy in women may include, but are not limited to: increase in acne, particularly cystic acne, increased urine output, fluid retention, androgenic alopecia (hair loss), changes to the lipid profile (decrease in HDL), increase in aggression, mood swings, and, in extreme cases, virilization. Virilization includes deepening of the voice, clitoromegaly, masculinization of body habitus, and androgenic alopecia. One study of postmenopausal women showed that a high testosterone-to-estrogen ration was correlated with a higher risk of heart failure and coronary heart disease, and higher levels of estrogen seemed to have a protective effect. However, this paper did not investigate testosterone supplementation on women and no hormone levels were measured prior to and during the menopausal transition.

· Acne and changes to the lipid profile occur with oral, but not transdermal and pellets of testosterone, and the available data suggest that androgenic side effects tend to be non-existent or mild with low doses of oral or transdermal testosterone. Compared with oral testosterone, transdermal testosterone has less effect in causing acne or hirsutism. The use of transdermal testosterone may be associated with some increase in acne, but it is not associated with any serious adverse events. The dose may be decreased to reduce this.

· Testosterone is category X (will cause birth defects) and should never be given to women who may become pregnant.

Contraindications for BHRT in general include: unexplained vaginal bleeding, severe active liver disease, prior estrogen-sensitive breast or endometrial cancer beyond stage II, coronary heart disease (CHD), stroke, dementia, personal history or inherited high risk of thromboembolic disease (DVT or other blood clots), porphyria cutanea tarda, or hypertriglyceridemia. Transdermal systemic estrogen may be safely used for those with history of strokes, clots, elevated triglycerides or clotting disorders.

Available alternatives to BHRT: There is always the option to forego BHRT. In such case, the risks of receiving no treatment if treatment is needed, include, but are not limited to: experiencing symptoms of hormone deficiency, and increased risk for age-related diseases or dysfunctions resulting from declining hormone levels. There is also the option of treating the symptoms of declining hormone levels as they develop with non-hormonal therapies such as herbal therapies, supplements, and lifestyle modifications such as weight loss, stress reduction, yoga, etc.

Please also note that transdermal hormones can be transferred to other people and pets through skin-to-skin contact or if the hormones get on surfaces touched by others. Patients receiving transdermal hormones must take care to prevent this. Please be sure to read and follow the instructions below to prevent transfer of your hormones to others:

· Thoroughly wash hands after applying transdermal hormones and before handling food products, animals, or small children.

· Do not allow children to make contact with the area where the hormone was applied. If contact with children cannot be avoided, wear a garment to cover the application site.

· If a child comes into direct contact with the skin where the hormone was applied, wash the child’s skin with soap and water as soon as possible.

· Do not allow pets to lick or touch the skin where the hormone was applied.

By taking Bioidentical Hormone Therapy prescribed by a medical provider, you confirm that you understand and agree to the following in order to receive BHRT from Effecty:

1. I have discussed the reason(s) for taking BHRT with my medical provider and why it is being recommended to me as a potential treatment choice.

2. I have disclosed all of my family and personal medical history requested by my medical provider(s) and recognize that this is extremely important for my safety in being prescribed BHRT.

3. I have no personal history or known risk for DVT (deep vein thrombosis), blood clots or stroke.

4. I have alerted my medical provider(s) if I have a personal or family history of breast, uterine (endometrial) or ovarian cancer.

5. I understand BHRT may not be safe and appropriate if I become pregnant. I will contact my medical provider immediately if I become pregnant.

6. I understand that the benefit-risk ratio appears less favorable if starting HRT 10 or more years after the onset of menopause or continuing it into the age of 60 and beyond because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Therefore, if I am choosing to start HRT 10 or more years after onset of menopause or choose to continue HRT into the age of 60 and beyond, I understand that there are potential additional risks that I am choosing to accept.

7. I understand the risks associated with taking hormones as described in this informed consent, and I understand that there are different risks if I also take progestogens or testosterone which may be higher or lower than taking estrogen alone.

8. I understand that spotting or bleeding can be normal in the first 3 months on the hormones. Any heavy bleeding must be evaluated. Any bleeding must be reported and discussed with my medical provider, as bleeding that recurs after a woman has completed menopause is one of the warning signs of possible uterine cancer. This will require further evaluation with a pelvic ultrasound and/or endometrial biopsy.

9. I am aware that unforeseeable complications could occur, and that while my medical provider will make every reasonable effort to screen for contraindications to BHRT and to decrease and minimize risks, I do not expect my medical provider to be able to anticipate and explain all possible risks and complications. I agree to report to my medical provider any adverse reaction or problems that might be related to my BHRT.

10. I further acknowledge that there may be risks of testosterone and or estrogen therapy that we do not yet know, at this time, and that the risks and benefits of this treatment have been explained to me and I have been informed that I may experience complications, including one or more of those listed above. I accept these risks and benefits.

11. I understand that initial lab testing will be performed to establish my baseline hormone levels. I agree to comply with my medical provider’s requirements for exams, follow-up consultations, lab-work and testing, and other screening exams in order to receive BHRT. I understand that BHRT refills may not be issued if the required testing and follow up reviews with my medical provider are not followed as prescribed.

12. I understand that I will be in charge of administering the hormones prescribed to me. I will comply with my prescribed doses and methods of administration. I also agree that if I am prescribed transdermal (topical) hormones, I will follow instructions to prevent transfer of the hormones to others including children and pets.

13. I understand my medical provider will not be my primary care doctor, and I agree that I am and will be under the care of a licensed physician for all of my primary care needs.

14. No Guarantees: I acknowledge that there are no guarantees or assurances made with respect to the benefit of BHRT prescribed for me. I understand that lifestyle modifications, proper nutrition and supplementation, adequate sleep and stress reduction are all key components to a successful BHRT regimen. Additionally, I understand that there is no guarantee that there will not be side effects or health complications from my use of BHRT.

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