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[159.112.244.18]) by mx.google.com with UTF8SMTPS id d75a77b69052e-50bb2f35854si35265651cf.280.2026.03.28.10.38.40 for (version=TLS1_2 cipher=ECDHE-ECDSA-AES128-GCM-SHA256 bits=128/128); Sat, 28 Mar 2026 10:38:40 -0700 (PDT) Received-SPF: pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.18 as permitted sender) client-ip=159.112.244.18; Authentication-Results: mx.google.com; dkim=pass header.i=@mg2.substack.com header.s=mailo header.b=Cf05UaGP; dkim=pass header.i=@mailgun.org header.s=mg header.b=rflHmpt+; spf=pass (google.com: domain of bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com designates 159.112.244.18 as permitted sender) smtp.mailfrom="bounce+a6cce7.4d1858-tjphuhs=gmail.com@mg2.substack.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=substack.com DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mg2.substack.com; q=dns/txt; s=mailo; t=1774719519; x=1774726719; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=SoI+ywQkNfiTHHtQeC6iuONNOxe6fSmxfe81eZCZurE=; b=Cf05UaGPZ2jHU92mymo3toHFMZSdeg569EV2fKzhXRf4IlxkiU9QIZiVv+IZpV2rhTk3nhEkaXW5dsk1aO0pAPqDCkLvR8hky3z5jrB22wGxbnFAqmi0qe+RZuDZuh3o6tKOfdZFHrdEOUE721j6bjUdeDl0YdFzlWtm6WCo4Yw= DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mailgun.org; q=dns/txt; s=mg; t=1774719519; x=1774726719; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=SoI+ywQkNfiTHHtQeC6iuONNOxe6fSmxfe81eZCZurE=; b=rflHmpt+7m3a4IEm86DRV+896qnT0prp0ARB52sb11NqaOZar4wrPG9NRrx7zf8hBj9gi6pr4f0aHnpu4HB5KMAaniqV+RjYHugzd7bJTnsYQutskiPy6rTbxmkDVOQnJw9nZQz/17yXBLLMUkn1TkPk90XjaB4rDPGAVNpiHeo= X-Mailgun-Sid: WyIxODZiYSIsInRqcGh1aHNAZ21haWwuY29tIiwiNGQxODU4Il0= X-Feedback-Id: postmaster@mg2.substack.com:post:5a78b6d5cd16820001f2a9d4:mailgun Received: by 5d8e7f3ace9b95e203776337c6ee8b262a0c398d300e6325b74d2a0b451cc56c with HTTP id 69c8121f277fbf794aaf2294; Sat, 28 Mar 2026 17:38:39 GMT X-Mailgun-Sending-Ip: 159.112.244.18 Mime-Version: 1.0 Content-Type: multipart/alternative; boundary="98353eae55d189bf8a7e0f22d7c5f9252dbac4404f9bb0fcf007d3f629b2" Subject: =?UTF-8?q?GLP-1_Pregnancy_Fears_vs_Reality=E2=80=A6_The_First_Real_Data_I?= =?UTF-8?q?s_In?= From: Dave Knapp from On The Pen To: tjphuhs@gmail.com X-Mailgun-Tag: post X-Mailgun-Track-Clicks: false Message-Id: <20260328173829.3.6ce8ae20b748b1aa@mg2.substack.com> Date: Sat, 28 Mar 2026 17:38:29 +0000 Feedback-Id: post-192437519:cat-post:pub-4808993:substack Sender: Dave Knapp from On The Pen References: In-Reply-To: Reply-To: Dave Knapp from On The Pen List-Owner: List-Url: List-Archive: List-Id: List-Post: List-Unsubscribe: List-Unsubscribe-Post: List-Unsubscribe=One-Click X-Mailgun-Variables: {"category": "post", "email_generated_at": "1774719519268", "is_freemail": "true", "post_audience": "everyone", "post_id": "192437519", "post_type": "newsletter", "pub_community_enabled": "true", "publication_id": "4808993", "subdomain": "onthepen", "user_id": "273622398"} --98353eae55d189bf8a7e0f22d7c5f9252dbac4404f9bb0fcf007d3f629b2 Content-Type: text/plain; charset="utf-8" Content-Transfer-Encoding: quoted-printable View this post on the web at https://onthepen.substack.com/p/glp-1-pregnanc= y-fears-vs-reality If you=E2=80=99re currently on a GLP-1, or if you=E2=80=99ve been on one lo= ng enough to feel your body experience massive changes, you already underst= and why this conversation matters. These are not casual medications for thi= s community, they are often the first thing that actually moved the needle = after years of trying everything else. For many others, it was the first re= al hope offered, after the promises of metabolic surgeries failed to delive= r as promised. That is exactly why pregnancy can add such a complex layer to the journey, = because the same medication that helped restore metabolic health is also re= storing ovulation in ways many women using GLP-1 therapies did not necessar= ily expect. For many in this community, pregnancy is no longer some far fet= ched possibility. Once those systems start functioning again, pregnancy bec= omes something that can happen much faster than the timeline you may have h= ad in your head. A new systematic review pulled together 36 human studies (over 2,000,000 pa= tients) looking at exposure to GLP-1 receptor agonists and dual incretin th= erapies like tirzepatide across preconception, early pregnancy, and postpar= tum. Most of the data comes from observational cohorts, so this is real wor= ld experience being analyzed, not tightly controlled clinical trials design= ed to answer one narrow question. Across those cohorts, early exposure, especially around conception and duri= ng the first trimester, was not consistently associated with increased risk= of major congenital malformations. When researchers adjusted for underlyin= g metabolic disease, outcomes like stillbirth, neonatal mortality, and feta= l growth restriction also did not show a reproducible increase compared to = similar patients treated with insulin or other therapies. That does not suddenly make this issue simple or risk free, and it is certa= inly not being presented that way in the literature. What it does do is sta= rt to chip away at the idea that early exposure automatically equals worst = case scenario, which is the exact question many patients and prescribers ha= ve quietly had in the back of their mind. Maternal outcomes were far less clean, and that part of the data feels exac= tly like you would expect at this stage. Rates of gestational diabetes, hyp= ertensive disorders, preterm birth, and gestational weight gain were all ov= er the place depending on the study, with no single direction that clearly = stands out. Where this really lands for the OTP community is with Polycystic Ovary Synd= rome, and this is not some small corner of the audience. This is a huge gro= up of women who have spent years being told their condition was secondary t= o weight instead of something with its own biology and its own set of lever= s. In the review, GLP-1 therapies were associated with improvements in both= metabolic and reproductive markers in women with PCOS, including signals a= round insulin resistance, hormonal balance, and in some studies, changes in= menstrual regularity and ovulation. These were often secondary outcomes ra= ther than primary endpoints, but the pattern showing up across studies is c= onsistent enough that it is getting harder to ignore. That is exactly where the data starts to line up with what this community h= as already been seeing in real life. There are countless stories of cycle r= egulation, improved ovulation, and in many cases unexpected pregnancies aft= er starting therapies like semaglutide or tirzepatide, and those stories ha= ve been piling up long before the data showed up on the scene. What is happening now is not that science suddenly discovered something new= , it is that it is finally starting to measure what patients have been repo= rting for years. That shift from anecdote to early structured evidence is s= low, but it is meaningful when you start to see the same signals show up in= both places.=20 You can see that shift even more clearly in how new trials are being design= ed. The PERIODS trial out of Germany is looking at tirzepatide specifically= for ovarian dysfunction, with ovulation frequency and menstrual regularity= as primary endpoints over a 72 week period, which is a very different ques= tion than most prior studies have asked. That matters because endpoints are how the system decides what a drug actua= lly does, and PCOS has historically been studied through indirect markers t= hat never fully captured the condition itself. When ovulation becomes the o= utcome, the framing starts to move closer to what patients have been descri= bing all along. Lactation is still largely an unknown, which is not surprising given how ea= rly this entire space is. There is one small pharmacokinetic study involvin= g Semaglutide [ chatgpt://generic-entity?number=3D3 ] that did not detect t= ransfer into breast milk, but the patient pool was small, and more studies = will likely be necessary for many clinicians to feel comfortable giving GLP= -1 use during lactation the =E2=80=9Cthumbs up=E2=80=9D. The biggest gap across all of this is duration, and that is where the uncer= tainty really shows up. Most of what we have looks at early exposure, not w= hat happens if someone stays on therapy throughout pregnancy, which leaves = the most obvious question is still sitting there unanswered. So what you are left with is not clarity, but context, and for this communi= ty that actually matters. Instead of operating in a complete vacuum, there = is now at least some human data suggesting that early exposure is not consi= stently tied to the outcomes people fear most, even though the full picture= is still being built. And that is really the point of this moment. The science is not finished, b= ut it is no longer silent either, and for a community that has been living = this in real time, that shift feels long overdue. I=E2=80=99m not a doctor, and this is not medical advice. I=E2=80=99m shari= ng what the data is starting to show and how it connects to what this commu= nity is experiencing. ALWAYS talk to your doctor about your own situation. Unsubscribe https://substack.com/redirect/2/eyJlIjoiaHR0cHM6Ly9vbnRoZXBlbi5= zdWJzdGFjay5jb20vYWN0aW9uL2Rpc2FibGVfZW1haWw_dG9rZW49ZXlKMWMyVnlYMmxrSWpveU= 56TTJNakl6T1Rnc0luQnZjM1JmYVdRaU9qRTVNalF6TnpVeE9Td2lhV0YwSWpveE56YzBOekU1T= lRFNUxDSmxlSEFpT2pFNE1EWXlOVFUxTVRrc0ltbHpjeUk2SW5CMVlpMDBPREE0T1Rreklpd2lj= M1ZpSWpvaVpHbHpZV0pzWlY5bGJXRnBiQ0o5LjNGU3VjRnJEdUdqSi0wbkh1SGhKRGJvYmUzcEx= vVERoV2RHT0Vac0c2QVkiLCJwIjoxOTI0Mzc1MTksInMiOjQ4MDg5OTMsImYiOnRydWUsInUiOj= I3MzYyMjM5OCwiaWF0IjoxNzc0NzE5NTE5LCJleHAiOjIwOTAyOTU1MTksImlzcyI6InB1Yi0wI= iwic3ViIjoibGluay1yZWRpcmVjdCJ9.9b_dEt4Mn9KZwB8jskzfJoeF3PyilliRCQtRsQXPTD4= ? --98353eae55d189bf8a7e0f22d7c5f9252dbac4404f9bb0fcf007d3f629b2 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable GLP-1 Pregnancy Fears vs= Reality… The First Real Data Is In3D""
If you’re currently on a GLP-1, or if you’ve been on one l= ong enough to feel your body experience massive changes, you already unders= tand why this conversation matters.
͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­
<= tr>
=
Forwarded this email? Subscribe here for more

GLP-1 Pregn= ancy Fears vs Reality… The First Real Data Is In

On The Pen GLP-1 News
<= /div>
<= tbody>
 
<= td style=3D"vertical-align:middle;">
3D""
3D""
3D""
3D""
<= /tbody>
READ IN APP3D""
 

If you’re cu= rrently on a GLP-1, or if you’ve been on one long enough to feel your= body experience massive changes, you already understand why this conversat= ion matters. These are not casual medications for this community, they are = often the first thing that actually moved the needle after years of trying = everything else. For many others, it was the first real hope offered, after= the promises of metabolic surgeries failed to deliver as promised.

That is exactly why pregnancy can add such a complex layer to the = journey, because the same medication that helped restore metabolic health i= s also restoring ovulation in ways many women using GLP-1 therapies did not= necessarily expect. For many in this community, pregnancy is no longer som= e far fetched possibility. Once those systems start functioning again, preg= nancy becomes something that can happen much faster than the timeline you m= ay have had in your head.

3D""

A new systema= tic review pulled together 36 human studies (over 2,000,000 patients) looki= ng at exposure to GLP-1 receptor agonists and dual incretin therapies like = tirzepatide across preconception, early pregnancy, and postpartum. Most of = the data comes from observational cohorts, so this is real world experience= being analyzed, not tightly controlled clinical trials designed to answer = one narrow question.

READ THE STUDY

That does not sud= denly make this issue simple or risk free, and it is certainly not being pr= esented that way in the literature. What it does do is start to chip away a= t the idea that early exposure automatically equals worst case scenario, wh= ich is the exact question many patients and prescribers have quietly had in= the back of their mind.

Maternal outcomes were far less cl= ean, and that part of the data feels exactly like you would expect at this = stage. Rates of gestational diabetes, hypertensive disorders, preterm birth= , and gestational weight gain were all over the place depending on the stud= y, with no single direction that clearly stands out.

Where = this really lands for the OTP community is with Polycystic Ovary Syndrome, = and this is not some small corner of the audience. This is a huge group of = women who have spent years being told their condition was secondary to weig= ht instead of something with its own biology and its own set of levers. In = the review, GLP-1 therapies were associated with improvements in both metab= olic and reproductive markers in women with PCOS, including signals around = insulin resistance, hormonal balance, and in some studies, changes in menst= rual regularity and ovulation. These were often secondary outcomes rather t= han primary endpoints, but the pattern showing up across studies is consist= ent enough that it is getting harder to ignore.

That is exa= ctly where the data starts to line up with what this community has already = been seeing in real life. There are countless stories of cycle regulation, = improved ovulation, and in many cases unexpected pregnancies after starting= therapies like semaglutide or tirzepatide, and those stories have been pil= ing up long before the data showed up on the scene.

What is= happening now is not that science suddenly discovered something new, it is= that it is finally starting to measure what patients have been reporting f= or years. That shift from anecdote to early structured evidence is slow, bu= t it is meaningful when you start to see the same signals show up in both p= laces.

You can see that shift even more clearly in how new= trials are being designed. The PERIODS trial out of Germany is looking at = tirzepatide specifically for ovarian dysfunction, with ovulation frequency = and menstrual regularity as primary endpoints over a 72 week period, which = is a very different question than most prior studies have asked.

READ ABOUT THE PERIODS TRIAL

That matters because endpoints are how the system decides what a= drug actually does, and PCOS has historically been studied through indirec= t markers that never fully captured the condition itself. When ovulation be= comes the outcome, the framing starts to move closer to what patients have = been describing all along.

Lactation is still largely= an unknown, which is not surprising given how early this entire space is. = There is one small pharmacokinetic study involving Semaglutide that did not det= ect transfer into breast milk, but the patient pool was small, and more stu= dies will likely be necessary for many clinicians to feel comfortable givin= g GLP-1 use during lactation the “thumbs up”.

READ ABOUT THE LACTATION STUDY

The biggest gap = across all of this is duration, and that is where the uncertainty really sh= ows up. Most of what we have looks at early exposure, not what happens if s= omeone stays on therapy throughout pregnancy, which leaves the most obvious= question is still sitting there unanswered.

So what you ar= e left with is not clarity, but context, and for this community that actual= ly matters. Instead of operating in a complete vacuum, there is now at leas= t some human data suggesting that early exposure is not consistently tied t= o the outcomes people fear most, even though the full picture is still bein= g built.

And that is really the point of this moment. The s= cience is not finished, but it is no longer silent either, and for a commun= ity that has been living this in real time, that shift feels long overdue.<= /p>

I’m not= a doctor, and this is not medical advice. I’m sharing what the data = is starting to show and how it connects to what this community is experienc= ing. ALWAYS talk to your doctor about your own situation.

=
=

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