Episode 257 – Peptides for Sexual Wellness & Hormonal Health: PT-141, Growth Hormones, Bone Health & More!

Dr. Deb Muth

0:00 Welcome back to Let’s Talk Wellness Now. I’m your host, Dr. Zab, and we are continuing our discussion this week on

0:08 peptides. And so, if you haven’t heard our first conversation about peptides,

0:13 please go back and look at that episode. We talk all about the manufacturing, the safety, the quality of peptides, and we

0:20 dove into GLP1s. And today we’re going to dive into peptides for sexual

0:26 wellness, immune function, growth hormone, and all the amazing fun things

0:32 we can do with peptides. So, as usual, grab your cup of coffee or tea, settle

0:37 in, and let’s talk wellness now. And we’re going to take a short pause from our sponsor. I know we’ve got to do

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1:10 Serenity Health. Because every queen deserves to feel in her prime. All

1:15 right, everybody. We are back. And are you ready? We are talking all things peptide and I am opening the show today

1:23 with sexual wellness. Yes, I’m going there, you guys. I am going there. You

1:29 know, this has really become a big issue for people um of all ages. It’s not just

1:3 4us older people. It’s younger people, too. And there’s a whole variety of reasons why we have sexual dysfunction.

1:42 And when we’re talking about sexual dysfunction, we’re not just talking about it doesn’t work, right? Or I can’t

1:48 reach orgasm. A lot of it is around desire and um the thought of it and

1:54 wanting to connect, wanting to be kinder to one another, wanting to be touching

2:00 one another. A lot of it resolves or revolves around that. And so there are some peptides that can help us and I’m

2:08 really excited to be able to talk about those today. So the first one is called PT-141.

2:14 This targets the brain not the periphery. Right? So for many women I

2:20 will always tell you sex starts between here. It is a brain thing for us. It is

2:26 not necessarily a physical thing. For guys that’s a little different. It’s very physical. For women it’s all in our

2:32 brain. So tip for you men that are listening. You have to prime your woman’s brain first if you want her to

2:38 have sex with you that night. You have to be nice to her. You have to bring her flowers. Do the dishes for her. Do

2:45 something kind. Bring her a cup of coffee or tea or a glass of wine. Take her to dinner. You have to woo her. And

2:51 I don’t care how long you’ve been married. That has to happen. And tip number two, don’t say anything stupid

2:57 that day. I’m just being honest. When you guys say things that make us upset,

3:03 that lingers with us for the rest of the day. And it’s it’s a turnoff for us. And

3:08 for a lot of women, we can’t get past that when it comes time to snuggle at night. And sex doesn’t always have to be

3:14 at night either. So, you can tell I really love talking about this conversation, but we’re going to get into the peptide part of it because this

3:21 is going to help people. So, um, PT-141 is marketed as I’m going to slaughter

3:28 this name, Vali, and it represents a fundamentally different approach to

3:34 sexual dysfunction than the PDE5s inhibitors like Slenden, Viagra,

3:40 Tedataphil, which is Seialis. And while the PDE5 inhibitors work specifically by

3:47 enhancing blood flow to the genital tissues, PT-141 works centrally in the brain by

3:54 modulating neural s neural circuits involved in the sexual desire and

4:00 arousal. Now PT-41 is a cyclic hpatipeptide. It’s seven amino acid

4:07 peptide arranged in a cyclic structure that acts as a melanoortin receptor

4:13 agonist and with particularly the infinity for MC3R and MC4R subtypes.

4:20 It’s actually a metabolite of the melanotan 2, a peptide originally

4:26 developed for tanning that was also found to enhance sexual desire in early

4:31 studies. Now the melanoortin system in the brain is involved in multiple functions including energy homeostasis

4:39 but it also is involved in sexual motivation and arousal behaviors. The FDA approved PT-141 in 2019 specifically

4:48 for the treatment of acquired generalized hypoactive sexual desire

4:54 HSDD in permenopausal women. So for the first time we have a medication that was

5:01 approved by the FDA to use for women for sexual dysfunction. We have had all of

5:07 these seialis tedataphil viagros for men but we had nothing for women. And so

5:12 this is amazing that this is available for women and approved by the FDA. It’s a big deal. This represents the first

5:19 and only FDA approved medication specifically targeting these circuits of sexual desire rather than the peripheral

5:27 arousal mechanisms. And this indication is quite specific, meaning it was developed at some point, not lifelong.

5:35 So I if you’ve had sexual dysfunction your entire life, this medication was

5:40 not approved for you. But if it’s something that you developed over time, like when you went through pmenopause or

5:46 menopause or some women have this experience happen after childirth, that’s what we’re talking about here.

5:53 Now, it’s also not just um supposed to be used if you dislike your partner,

5:59 right? If your relationship is bad and you dislike your partner, this probably isn’t going to fix a ton. It might help

6:05 a little bit, but that’s not what it’s meant for. So, you really have to know what you’re using it for and why. And

6:11 the other thing that I would say is this is something that we don’t go to if your hormones are not balanced properly. You

6:17 have to balance your hormones properly before using something like this because it still may not work. Now, the only

6:24 caveat to that is if you’re a woman that has a risk of breast cancer and can’t use hormones, then that’s a different

6:31 story and we would have that conversation about whether or not this medication would be appropriate for you. Now, the FDA label specifies PTA1 uh

6:39 PT-141 as it not being indicated for HSDD in causes where low sexual desire

6:46 is due to coexisting medical or psychiatric conditions, problems with relationships, like we had talked about,

6:53 side effects to medications or other substance use. This specifically reflects the importance of differential

6:59 diagnosis. Low sexual desire can have many root causes and PT-41 is only

7:05 appropriate when those causes have been ruled out. Now, I have I used PT41 in

7:10 people who have sexual dysfunction issues as a result of using

7:16 anti-depressants. Yes, I have. I’ve used Flynn in that effect as well. And it

7:21 does work sometimes, but it doesn’t work completely. But you need to know that that is not what the approval is for the

7:27 FDA. So that is done in something that we call off label use. So very important

7:33 to know. Now in these clinical trials leading to FDA approval, this was published by Kinsburg and colleagues in

7:40 obstetrics and gyne gynecology in 2019. PT-141 demonstrated statistically

7:46 significant improvements in sexual desire and decreases in distress related

7:51 to low desire compared to placebo. The effects manifest over 45 minutes to

7:56 several hours after the injection and the mechanisms involved modulation of dopamine and melanoorton pathways in the

8:04 hypothalamus and the brain regions that involved sexual motivation. Now cardiovascular effects of PT 141 require

8:12 careful attention. This drug causes transient increases in blood pressure about 3 to four points and transient

8:20 decreases in heart rate. And because of this, it is contraindicated in patients

8:25 with uncontrolled hypertension or known cardiovascular disease. And it has been studied in patients who’ve had recent

8:32 cardiovascular events or sorry hasn’t been studied hasn’t been studied in patients who’ve had recent

8:39 cardiovascular events. So patients need to have their blood pressures checked before starting therapy. Nausea is

8:45 extremely common. It is one of the biggest things I often will tell people to take an anti-nausea medicine if

8:52 they’re going to do this because the last thing you want to do is inject this medication and think it’s going to give

8:57 you this great time with your partner and you’re so nauseated that you can’t even perform, don’t want to kiss, don’t

9:05 want to do anything. It it can be pretty profound for some people. um it does affect about 40% of the patients in

9:12 clinical trials which is why many clinicians require or recommend an

9:17 anti-nausea medication like I had just said other common adverse effects include flushing injection site

9:24 reactions headache in about 13% of the population which I have seen worse if

9:30 people are prone to headaches and the headaches are pretty intense so I will also have them premedicate if they have

9:36 that um sensitivity ity with a Tylenol or Advil, Alie, whatever it is they

9:42 typically use for their headaches to help prevent that from occurring. Now, some patients also experience a

9:50 generalized hyperpigmentation of their skin, particularly in areas with chronic friction, and this may not be reversible

9:57 after discontinuation. So from an integrative perspective, PT-41

10:03 represents one tool in addressing female sexual dysfunction, but it should never be the first or only intervention. And

10:11 low sexual desire in women is complex. Multiffactorial involving hormonal imbalances, low testosterone, estrogen

10:18 deficiency, progesterone imbalances, thyroid dysfunction, adrenal dysfunction, and with elevated or

10:24 disregulated cortisol levels, sleep deprivation, relationship issues, unresolved trauma, including sexual

10:31 trauma, chronic pain, body image concerns, and medication side effects such as SSRIs are notorious for this. So

10:39 a comprehensive hormone panel including total and free testosterones, estradile,

10:45 progesterone, DHEA, thyroid function in cortisol assessment, ideally four-point

10:51 cortisol, salivary should precede any pharmacological intervention. And additionally, addressing the

10:57 psychological component and relationship dimensions through appropriate therapy is necessary. I have a lot of patients

11:03 that say, “This is just too much work for sex. I don’t want the side effects. I don’t want to deal with this.” and that’s totally fine. But for some

11:09 people, their sexual dysfunction is actually causing more problems on their

11:14 relationship and they want to do something to fix that. And just know that if you’re using a peptide like this

11:20 that comes with some of these side effects and you have to premedicate for it, it is not the end of the world. Um,

11:27 but it may be a possibility that you may need that. So, let’s dive into body composition and growth hormone access.

11:34 So Tesmarellin is the only FDA approved GH

11:40 analog. Tesarelin is marketed as Agrifta and Agria SV. It is a synthetic analog

11:48 of human growth hormone releasing hormone. So GH RH human growth hormone

11:53 releasing hormone. These things are such long names it’s confusing and it’s difficult to spit out, right? It

11:59 consists of 44 amino acids. The structure is identical to our own

12:05 body’s growth hormone GHR um with the addition of trans3 hexonol group which

12:14 stabilizes the molecule that extends its half-life compared to the native GHR.

12:19 The mechanism of tesmarellin is elegant in its preservation of physiological

12:24 growth hormone GH secretion patterns and rather than administering an exogenous

12:30 growth hormone directly, tesmarillin binds to the GH receptor in the anterior

12:36 pituitary gland stimulating the indogenous pulsatile release of GH. So

12:42 you know it it’s slower in that stimulation and it pulsates instead of a direct rise and fall. This pusile

12:49 pattern more closely mimics natural GH secretion which occurs in bursts

12:54 primarily during sleep. The GH then stimulates the liver to produce insulin-like growth factor IGF-1 which

13:01 exerts many of the downstream metabolic effects including lipolytic effects on

13:07 the atapost tissue. So fat atapose and how we break that down. The FDA approved

13:13 tesmarellin in 2010 for a very specific narrow indication, the reduction of

13:19 excess abdominal fat in HIV infected patients with lipodistrophe. This

13:25 condition characterized by abnormal fat redistribution with accumulation of visceral body fat and the loss of

13:32 subcutaneous fat in face and limbs developed as a complication of an

13:37 antiviral therapy particularly with older protease inhibitor reg uh

13:42 regimens. The visceral fat accumulation in patients is not just cosmetic. It’s associated with increased cardiovascular

13:49 risk, insulin resistance, and inflammatory markers. The pivotal trial that led to the FDA approval included

13:56 work by Stanley and colleagues published in the annuals of internal medicine in 2014. It demonstrated that tesmarillan

14:03 significantly reduced the visceral atapose measured by CT scan by approximately 15 to 20% which is a

14:10 significant difference to placebo over a short period of time only 26 weeks. Now,

14:16 interestingly, the total body uh weight typically remained stable or even

14:21 increased slightly as the reduction of visceral fat was sometimes offset by increases in lean body mass or

14:28 subcutaneous fat. This highlights an important point. Tesmearellin is not a weight loss drug in its conventional

14:34 sense. Its effects are specifically on body composition and fat redistribution.

14:40 Now the glucose metabolism effects of tesmarellin do require careful monitoring because GH and IGF1 can

14:47 induce insulin resistance. Tesmearellin can increase glucose levels and hemoglobin A1C and in these clinical

14:54 trials glucose tolerance and new onset diabetes occurred in some patients. So

14:59 this creates a therapeutic paradox while res reducing visceral fat we should theoretically improve metabolic health.

15:07 The GH mediated insulin resistance can worsen the glycemic control and patients

15:12 with diabetes require particularly close monitoring. The potential need for adjustment in diabetic medications can

15:19 occur. So I already know what you guys are thinking. Can I use Tesmarellin and

15:24 GLP1 at the same time? And the answer is yes. Especially in those people that we

15:30 know have an insulin resistance already or are prone to that, we can use lowd

15:36 dose micro doing GLP-1 along with tesmarellin to help prevent this from

15:42 occurring um or reduce the risk of it occurring. Now there are some other adverse related problems to growth

15:49 hormone access which include fluid retention which can uh manifest as uh

15:55 ankle swelling, joint pain, muscle pain, paristhesas, carpal tunnel syndrome is

16:01 common to see. Of course you can always see injection site reactions reported about 26 to 30% of the time in the trial

16:08 participants. And this also theoretically has a concern about IGF-1 elevation potentially promoting

16:14 malignancy through long-term data is limited. So we have to be cautious about

16:20 this but it is a growth hormone and anything that is a growth hormone can cause cells to grow and it cannot

16:26 necessarily differentiate between healthy cells and bad cells. So the drug is contraindicated is contraindicated in

16:33 patients with active cancer and in patients with the disruption of the HPA access from conditions like pituitary

16:40 tumors, pituitary surgery, head of radiation um and traumatic brain injury.

16:46 Now off label use of tesmarellin for general anti-aging or body composition

16:51 optimization in non-HIV population, it doesn’t have FDA approval. There is no

16:58 FDA studies. um that promote this, but practitioners do prescribe it for these

17:04 purposes under an experimental and not supported by FDA approved indications.

17:10 And um from an integrative medical standpoint, optimizing natural growth

17:15 hormone secretion through lifestyle interventions, high quality sleep is important. GH primarily is excreted

17:22 during sleep and deep sleep waves. So improving your deep sleep is important. Intermittent fasting can also increase

17:28 growth hormone by five-fold as demonstrated in a Hartman and colleagues uh study from the journal of clinical

17:35 endocrinology and metabolism in 1992. And highintensity interval training, adequate dietary protein, blood sugar

17:42 control, these all can help naturally increase your growth hormone. So, let’s

17:47 dive in now and talk about bone health. peptide hormones um such as oh I’m gonna

17:54 I’m gonna really slaughter this name. Terraparatide is a true bonebuilding

18:01 peptide. It’s marketed as forio. It’s a recumbent form of the first 34 amino

18:08 acids out of 85 of the human parathyroid hormone PTH. It represents a unique

18:13 approach to osteoporosis treatment because it’s one of the few truly anabolic anabolic bone therapies meaning

18:21 it actively binds new bone rather than simply preventing bone loss. The biology

18:26 of parathyroid is fascinating and seemly contraindicated or uh contradictory.

18:32 Continuously sustained elevations of PTH as occurs in hyperarathyroidism

18:37 is catabolic to bone. So people who have hyperarothyroidism typically have significant bone loss

18:44 especially before it’s diagnosed and it causes causes increased bone

18:49 reabsorption loss of bone density increased fracture risk and however

18:55 intermittent exposure to PTH as achieved with once daily uh injections of forio

19:01 has the opposite effect. This intermittent exposure preferentially stimulates osteoblasts bone building

19:08 cells over osteoclasts bone reabsorbing cells and it leads to

19:13 the net bone formation. So terraparatide binds to the PTH receptors on

19:20 osteoblasts and renal tubular cells in bone. It increases the number of

19:25 activity of osteoblasts stimulating the differentiation of osteoblast precursor cells and may

19:32 reduce osteoblast apoptosis basically programmed cell death allowing this bone

19:37 building cell to work longer. The result is increased bone formation, improved bone architecture and tbacular

19:45 connectivity and ultimately increased bone mineral density um particularly in the hip and the spine which is so

19:51 difficult to regain. The FDA approved this medication in 2002 based on pivotal

19:57 studies by Near and colleagues published in the New England Journal of Medicine in 2001 which demonstrated significant

20:05 reductions in vertebral and non-vebral fractures in post-menopausal women with

20:11 osteoporosis. specifically uh reduced new vertebral fractures by

20:17 65% and nonvettebral fragility fractures by 53%

20:23 compared to placebo over a median followup of 21 months. This is really

20:29 incredible because we have not seen this kind of um change uh in other

20:35 medications that we’ve used for osteoporosis. So current FDA approval

20:40 indicates uh this for post-menopausal women with osteoporosis at high risk for

20:46 fracture, men with primary or hypoconatal osteoporosis at high risk for fracture

20:53 and men and women with glucocord cord glucocordide

21:00 induced osteoporosis at high risk for fracture. The high risk qualifier is

21:05 important. uh terrapeptide is reserved for patients with severe osteoporosis,

21:11 multiple fractures, very low low bone density and those who have failed or are

21:16 intolerant of other therapies. The most significant concern for this medication

21:21 is highlighted in a boxed warning with rat toxicology studies where it caused

21:27 osteioaroma which is a bone cancer in a dose dependent and treatment duration dependent manner. The revolence of this

21:34 finding to humans is debated. Rats have fundamentally different bone biology than humans with continuous bone growth

21:41 throughout life and different PTH receptors. Now post marketing

21:46 surveillance in humans hasn’t shown a clear increase in osteocaroma risk but

21:51 theoretically concerns persist and because of this terapeptide is

21:57 contraindicated in patients at risk baseline risk for osteioaroma

22:02 including those with pageantss disease of the bone unexplained elevations of alkaline phosphate prior skeletal

22:10 radiations bone metastases or skeletal malignancies and pediatric patients or young adults

22:16 with open hyes. There’s also a lifetime treatment duration of only 2 years and

22:22 terrapeptide can cause transient hypercalcemia. So an elevated blood calcium and as PTH normally increases

22:31 calcium levels by enhancing bone reabsorption, increasing renal calcium

22:36 reabsorption and promoting activation of vitamin D which increases intestinal calcium absorption. Some patients

22:43 experience orthostatic hypotension within 4 hours of injecting requiring

22:48 caution in at risk populations for blood pressure. Common side effects include

22:53 muscle pain, joint pain, pain in the limbs, nausea, headache, and dizziness. So from an integrative bone health

23:00 perspective, terrapeptides should be part of a comprehensive strategy. Adequate calcium intake, 500 to a,000

23:08 milligrams of calcium a day from food and supplements combined. and vitamin D.

23:13 Getting vitamin D levels of at least 50 to 80 are essential for the drug to work

23:20 optimally. But beyond this, bone health requires vitamin K2, which directs calcium into the bones rather than soft

23:27 tissues, magnesium as a co-actor in bone metabolism, trace minerals like boron,

23:33 copper, silica, and of course, adequate protein intake, which many of us, especially as women, don’t do 0.8 8 to 1

23:42 gram of protein per kilogram of body weight, weightbearing exercise. Of

23:47 course, these all provide mechanical signals that complement the biochemical

23:52 symbol uh signals of terrapeptide. Sequential therapy is also critical. The

23:58 bone mass gains from terraparatide can be lost if patients don’t transition to

24:05 an anti-resorbbitive agent a bisphosphinate after completing this therapy and the anabolic effects to

24:12 build bone but maintaining the new bone requires preventing excess reabsorption.

24:18 So positive things about this but there are definitely some concerns as well. So

24:23 the next one we’re going to talk about is Lu Prolrooide. It is marketed under

24:29 the multiple brand names of Lupron, Depo, Eligard, and it’s a synthetic

24:34 nonapeptide analog of naturally occurring ginonadotropen releasing

24:39 hormone G&R, also called luteinizing hormone releasing hormone, LHR.

24:46 It’s a fascinating example of how manipulating natural hormonal feedback systems can create therapeutic effects.

24:53 So, G&RH is normally secreted in a pulsatile fashion by the hypothalamus

24:59 and travels to the anterior pituitary where it binds to G&R receptors and

25:05 stimulates the release of luteinizing hormone LH and follical stimulating hormone FSH. These ginatotropins signal

25:13 the ovaries or the testes to produce sex hormones, estrogen, progesterone in

25:18 women, testosterone in men. Uh, luoprololi lupron as a GNR agonist

25:26 initially mimics the action of natural G&R causing an acute flare response with

25:33 uh increased LHFSH secretion which temporarily increases sex hormone

25:38 production. However, the continuous administration which is in the depo

25:44 formulations, the GNR receptors in the pituitary become desensitized and

25:50 downregulated. And after about 2 to four weeks of continuous exposure, LH and FSH

25:56 secretion is profoundly suppressed, leading to what’s termed as chemical

26:01 castration. Testosterone levels in men drop to castrated levels less than 50

26:08 and estrogen production is marketkedly suppressed in women. This bifphasic

26:13 response creates both therapeutic applications and management challenges in prostate cancer where tumor growth is

26:20 typically androgen dependent and the ultimate goal is testosterone suppression. However, the initial

26:27 testosterone surge during the flare phase can temporarily worsen symptoms potentially causing increased bone pain,

26:34 urinary obstruction, or even spinal cord compression in patients with metastatic

26:40 disease. This is why uh luoprolide is often started with an anti-ad androgen

26:47 like bicladamide for the first two to four weeks to block the effects of the

26:52 testosterone surge. The FDA has approved lupalide for multiple indications across

26:59 formulations. In oncology, it’s used for palletive treatment of advanced prostate cancers. In gynecology, various

27:06 formulations are approved for endometriosis, for pain management and lesion reduction and for fibroids.

27:13 Typically for pre-operative uh hematological improvement in anemic patients. In pediatrics, it’s used for

27:20 central precocious p puberty basically to halt the premature sexual development of these young people. Now, there are

27:28 adex uh adverse effect profile that reflects profound hormonal suppression.

27:34 In men treated for prostate cancer, hot flashes affect about 59% of the patients. Other common effects include

27:41 general pain, swelling, bone pain. Um long-term use of these medications leads

27:47 to metabolic changes. It increases fat mass. It decreases lean mass. It worsens

27:53 insulin sensitivity, disrupts the cholesterol uh lipid panels, increases

27:59 diabetic risk, has some concerns over cardiovascular disease. And the metaanalysis have shown increased risks

28:06 of heart infarction, myocardial inffection, sudden cardiac death, and stroke in populations receiving

28:13 long-term androgen deprivation therapy. The bone effects are particularly dramatic. Without sex hormones, bone

28:20 density decreases significantly, typically 3 to 4% per year during the

28:26 first two to three years of therapy. And this bone loss may not fully be reversible after the the therapy

28:32 discontinues. The American Society of Clinical Oncology recommends bone density monitoring and consideration of

28:39 bisphosphinates uh in men receiving long-term androgen deprivation. In women treated for

28:46 endometriosis or fibroids, the estrogen suppression creates a hypoestrogenetic state similar

28:54 to menopause. Hot flashes affect 90% of patients with other common effects

29:00 including headaches, emotional irritability, decreased sex drive, vaginal dryness, bone density loss. And

29:08 because of these bone concerns and treatment duration with endometriosis, typically limited to six months, though

29:14 some formulations allow for longer use with adback hormonal therapy to

29:20 partially mitigate these side effects. The mood and cognitive effects can be s

29:25 significant. I’ve seen it over the years. the depression, the memory impairment, difficulty focusing and

29:31 concentrating. It can be very very traumatic and the quality of life that

29:37 happens for these uh women and men can be unbearing for many of them. Um, from

29:44 an integrative perspective, patients receiving this medication need comprehensive support care. Bone health

29:51 interventions using calcium, vitamin D, vitamin K2, weightbearing exercise,

29:58 cardiovascular risk management becomes critical, including blood pressure monitoring, lipid management, diabetes

30:05 screening. For hot flashes management, some patients respond to black coohos,

30:10 sage, or vitamin E. Though evidence is mixed and individual response varies,

30:16 omega-3s may help with the mood and the inflammation, resistance training becomes specifically important to

30:22 preserve lean muscle mass in the face of hormonal suppression.

30:27 Now there’s something called calcetonin salamon which is marketed as miaelin.

30:34 It is a nasal spray. It is now discontinued. And foral is the new

30:39 synthetic polyeptide hormone of 32 amino acids identical to calcetonin of salamon

30:47 origin. It represents an interesting case study in how initial promise gives

30:52 way to safety concerns that regulate a therapy to historical footnote status.

30:58 Calcetonin is naturally occurring hormone in humans. It’s secreted by the paraphalicular sea cells in the thyroid

31:04 gland. Its primary physiological role is to lower blood calcium levels by

31:10 directly inhibiting osteoclast activity, reducing bone reabsorption, increasing

31:16 renal calcium secretion or excretion, and possibly reducing the intestinal

31:21 calcium absorption. So, salamon calcetonin is used therapeutically because it’s more potent and longer

31:27 acting than human calcetonin. The FDA initially approved calceton and salmon

31:34 for several indications post-menopausal osteoporosis in women more than five

31:39 years post-menopausal when alternative treatments are not sustainable. Padet’s

31:44 disease for bone and hypercalcemium as emergency treatments. The nasal spray formulation is particularly popular for

31:53 osteoporosis because it offered a non-injectable alternative to bisphosphinates.

31:58 However, in 2012, the European Medicine’s Agency, EMA, conducted a

32:05 comprehensive safety safety review after a poolled analysis of 21 clinical trials

32:10 involving over 10,000 patients showed a statistically significant increase in

32:15 malignancy risk in patients treated with calceton salamon compared to compared to

32:21 placebo. The overall malignancy rate was 4.1% in calcetonin treated patients

32:28 versus 2.9% in placebo patients. The types of cancer

32:34 varied with no single cancer type predominating, making it difficult to establish a clear mechanistic link.

32:41 However, the signal was concerning enough that the EMA restricted the use of calcetonin containing medicines. In

32:48 the United States, the FDA issued communications about malignancy signal and conducted its own review. While they

32:56 didn’t fully withdraw the drug, the cons consensus shifted dramatically. The nasal spray formulations miaelson was

33:03 voluntarily discontinued by the manufacturer and current clinical practice guidelines now consider

33:10 calcetonin salamon as a second line or lower option for osteoporosis. While

33:15 behind bisphosphinates, dennism mob, uh, terrapeptide, the analesic effect of

33:21 calcetonin in bone pain, particularly in acute vitibbral, uh, compression

33:26 fractions from osteoporosis or pageantss disease may still provide a role for short-term use in these selected

33:32 patients. The mechanism of this pain relief is unclear, but may involve

33:38 effects of endorphin systems and/or direct actions on pathways. The history serves as an important reminder in

33:45 peptide medicine. Initial approval and early clinical use does not guarantee

33:50 long-term safety effects. Post marketing surveillance and poolled analysis of the clinical trial data can reveal adverse

33:58 effects that weren’t apparent in initial studies. It also underscores why newer

34:04 agents with better safety profiles um have largely replaced calcetonin in

34:10 clinical practice. So this is really an important thing. Not one thing stays the same forever. We have to change as we

34:18 identify new and better products as we identify problems and concerns. I will

34:24 always tell my patients if you are uncertain of taking a new drug which we

34:30 all should be wait five years. Within five years we are going to find the

34:36 problems that they didn’t find in the clinical studies. Remember, a lot of these clinical studies are small, small

34:43 groups, short periods of time. It’s expensive to do these trials. So, if you

34:49 wait for five years, in the first two to three years, you will see the problem start to emerge. And what are you going

34:55 to look for? You’re going to look for the the news um commercials from lawyers

35:02 suing a drug. And they will tell you what the problem is. and then you can decide, is this something that I want to

35:09 use or not. Don’t jump on bandwagon and be the first one to do this, especially

35:14 if you’re sensitive. You know, give it time so you can see exactly what’s going on. So, I’m going to end our show on

35:22 this and we are going to pick up on part three of peptide therapy in our next

35:28 segment where we’re going to talk about the investigational peptides and some

35:34 exciting things that are happening with that. So, I want to thank you for joining me today on Let’s Talk Wellness

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36:21 educational purpose for everybody else. I love doing it, but it really helps us

36:28 on the algorithms if you would be just willing to like, subscribe, and share.

36:33 So, thank you for spending your time with me. I know time is important.

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