Cyclic Progesterone Therapy for PCOS

Progesterone has beneficial anti-androgen properties and can help to promote ovulation. That makes progesterone potentially therapeutic for polycystic ovary syndrome, as described in my recent paper The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS)—Evidence for treatment with cyclic progesterone.

Progesterone is real progesterone, also called body-identical progesterone or oral micronized progesterone (OMP), which is available as products such as Prometrium, Utrogestan, Teva, and Famenita, depending on your country. Progestins, on the other hand, are not progesterone and do not exert the same ovulation-promoting effect. And although some progestins (eg. drospirenone) are anti-androgenic, others (eg. levonorgestrel) are androgenic or testosterone-like and can worsen the androgen excess and insulin resistance of PCOS.

PCOS begins in the brain

Most evidence points to a “neuroendocrine” basis to PCOS which means that dysfunction in the brain, or more specifically, in the hypothalamus is the main cause of ovarian androgen excess. It works like this:

In a normal, healthy menstrual cycle, the hypothalamus releases pulses of GnRH (gonadotrophin-releasing hormone), first slowly, then more rapidly, then slowly again after ovulation. In turn, those pulses stimulate pituitary hormones (FSH and LH) that coordinate ovulation and promote the healthy production of estrogen and progesterone. A key feature of a healthy neuroendocrine system is progesterone’s beneficial slowing effect on the GnRH pulses. In other words, progesterone (made by ovulation) exerts beneficial negative feedback on the hypothalamus thereby lowering androgens and promoting future ovulation.

Normal GrRH pulsatility
Normal GnRH pulsatility promotes ovulation and progesterone.

With PCOS, rapid GnRH pulses result in chronically elevated LH, androgen excess, insulin resistance, and ultimately, progesterone deficiency due to anovulation. As illustrated in this image from the 2019 paper Neuroendocrine impairments of polycystic ovary syndrome.

Abnormal or high GnRH pulsatility causes PCOS
Abnormal or high GnRH pulsatility causes PCOS.

Unfortunately, progesterone deficiency then promotes a vicious cycle of impaired feedback on the hypothalamus, leading to persistently rapid GnRH pulses and further anovulation.

👉🏽 Tip: The original cause of the rapid GnRH pulses of PCOS is believed to be a combination of genetics and epigenetics resulting from in utero exposure to androgens and environmental toxins. High insulin or insulin resistance also contribute to rapid GnRH pulsing.

Cyclic progesterone therapy to the rescue

According to Professor Jerilynn Prior (co-author of the paper), “cyclic progesterone therapy means treatment with the natural progesterone hormone (oral micronized progesterone, Prometrium® or compounded in oil) in a way that mimics the normal pattern (14 days in the last half of the menstrual cycle) and amount (300 mg at bedtime).”

In our paper, Professor Prior and I explain the four mechanisms by which cyclic progesterone therapy can improve androgenic PCOS:

  • Cyclic progesterone induces regular withdrawal bleeds and can prevent endometrial hyperplasia, atypia, and endometrial cancer. (Tip: If cyclic progesterone does not induce a withdrawal bleed, it’s probably not PCOS.)
  • Cyclic progesterone reduces dihydrotestosterone (DHT), the active form of testosterone thus relieving acne, hirsutism, and androgenic alopecia.
  • Cyclic progesterone increases metabolic rate and can assist with weight loss.

And most importantly:

  • Cyclic progesterone “addresses the central pathophysiology of androgenic PCOS by slowing the pulse frequency of both GnRH and LH to allow normal FSH and follicle growth and to promote normal reproductive cyclicity, ovulatory menstrual cycles, and fertility.”

By normalizing GnRH pulsatility and lowering androgens, cyclic progesterone therapy can also help to improve insulin resistance.

How to take cyclic progesterone therapy

Some of my PCOS patients have had success with cyclic progesterone at a lower dose of 100 mg at bedtime. (Taken cyclically two weeks on, two weeks off.)

👉🏽 Tip: It’s best to take progesterone at bedtime because oral progesterone can be very sedating. Taking it during the day can cause grogginess and depression.

If cycles are irregular and anovulatory, the starting dose is two weeks on and two weeks off until regular ovulation can be established.

Once cycles are ovulatory, it’s best to switch to taking progesterone only during the two weeks of the luteal phase (ie. starting a day or two after ovulation).

To obtain oral micronised progesterone, you’ll need a prescription from your doctor. You could try saying:

“Could I please try a few months of Prometrium for PCOS? According to this Canadian endocrinology professor, progesterone can induce a withdrawal bleed and improve androgen symptoms.”

Show your doctor a printed copy of our paper The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS)—Evidence for treatment with cyclic progesterone and say you “would like to trial it for three months.” If your doctor is hesitant, offer to leave it with her and return for a second appointment. (Email me for a PDF copy of the full paper.)

Is progesterone safe?

Unlike progestins which are associated with mood side effects and an increased risk of breast cancer, body-identical progesterone is safe. For example, progesterone is usually beneficial for mood and sleep, and according to Professor Prior, natural progesterone may even help to reduce the risk of breast cancer.

As discussed in my Guide to progesterone blog post, cyclic progesterone therapy can also be helpful for perimenopause, heavy periods, endometriosis, adenomyosis, migraines, and premenstrual mood symptoms including PMDD.

In conclusion, cyclic progesterone therapy is potentially beneficial for PCOS. It can be safely combined with other PCOS treatments such as metformin, spironolactone, and inositol. Ask me in the comments.

55 thoughts on “Cyclic Progesterone Therapy for PCOS”

  1. Hi Lara, I can only get hold of 200mg or 400mg of oral progesterone so unable to take 300mg each night.

    Please let me know if I am best to start with the lower dose of 200mg or 400mg? 2 weeks on and 2 weeks off. I do not have periods but have hirtuism so keen to see if this helps.

    Thanks

    Reply
  2. Hi Lara, I’ve recently read your period repair manual. I’ve stage 4 endometriosis with recurring endometriomas. I’ve had 3 surgeries in past 4 years. My gynecologist wanted to give me monthly injections to suppress my hormones (temporary menopause) so to prevent another surgery in the short term. I wasn’t prepared to do this and asked him to prescribe me micronized progesterone instead (utrogestan) as I read about this in your book. I’m currently taking serval supplements; DIM, milk thistle, vitex, NAC, zinc, magnesium & vit b complex, tumeric and fish oils. Would any of these affect the micronized progesterone or visa versa?

    Reply
  3. Lara, I’ve battled with PCOS from the time I was 14 and diagnosed at 16. Now 37, I still barely get my periods (may be once a year if anything) The last time I had my period was 1.5 years ago.

    I’ve tried a number of things to become healthy so my periods would return properly but I’ve had little success. The longest I’ve not had a period was 12 years (from 14 yrs – 26 yrs of age).

    I recently read some material from you where you mentioned there are different types of PCOS. I also tried your suggestion to take some progesterone for 2 weeks, and if I didn’t get my period after, it may not be PCOS.

    I feel like I have the symptoms that I’m getting my period, but nothing happens. My husband and I desperately want a baby and need some guidance please.

    This is my current supplement/care routine:

    – myo-inositol

    – NAC

    – vitamin b12

    – vitamin d

    – vitamin c

    – evening primrose oil

    – paused taking vitex as I felt like i was putting on weight

    – paused taking chinese herbs from my acupuncturist

    – Anna’s Wild Yam progesterone cream ( stopped 16 Nov 2021)

    – weekly Chinese acupuncture for PCOS

    What am I doing wrong? I feel so distraught and would appreciate some guidance.

    Thank you in advance.

    Reply
  4. Hi Lara,
    Thank you for this – I’m desperate to try this as I’ve had anxiety for years and PCOS which has worsened post my two babies – struggling with the second half of my cycle and feeling wired but tired, fatigued, anxious, and bad acne along jawline.. as well as trouble losing weight around abdo!

    I spoke to my GP and shared the paper but she doesn’t want to presivrbe as she says it’s high dose ans I carry a prothrombin gene mutation – but wants me to try the pill or metformin.. it’s so hard is ther any evidence around risks of blood clots with the Prometrium?
    Thank you 😊

    Reply
    • Oral micronized progesterone (Prometrium) does not increase coagulation or the risk of venous thromboembolism. In fact, it’s safer than the pill.

      Reply
  5. My 16 year old daughter had one period at 14 and then nothing. About 9 months ago, she was started on progesterone (not bio-identical) and that induced bleeds, but she had all the PCOS symptoms and became terrified she would never be able to have children. We began following the protocol in your book (dairy (except for butter and ghee) gluten, and sugar free, magnesium, inositol, Rosita cod liver oil, prebiotic, zinc), lower carb except for dinner. It’s been about three months and she still doesn’t have a period. If she tries bio-identical progesterone, will it bring on a period and make her fertile? Is it something she would have to take forever or is there a possibility her body will eventually heal and begin to ovulate on its own?

    Reply
  6. If i was to do cyclic progesteron therapy for PCOS (i have androgen excess with no periods) would i take 100mg or 300mg at night? How do i know the right dose?
    Thanks

    Reply
  7. Hi Dr. Briden,

    In your experience, how long does it take to re-establish ovulation using this method? Also, once it is reestablished, should the progesterone be continued indefinitely throughout the ovulatory years? Or at a certain point does one see whether their own ovulation takes over? Thank you!

    Reply
  8. Hello! I appreciate your work and admire your knowledge.
    I have microcystic ovaries, HOMA IR 2.4, free testosterone 1.5%, SHBG 114 nmol/L, FSH 7.4 IU/L, LH 8.05 IU/L,estradiol 147 pmol/L – all in folicular phase. Also I have acne and bad PMS.
    What should I use for balancing my cycles? Thank you!

    Reply
  9. Hi Lara! I hope that you read me🙏
    Im having endo excision surgery and hysterectomy tomorrow and I’m worried of what will happen with my hormones afterwards. I know my ovaries will continue doing their job but have rear that they can be shut off for a few weeks following the histerectomy.
    I’ve also been taking geslutin for over a year on P+3-P+12 based on creighton charting but without bleeding I don’t know how I would track that anymore.
    I was wondering if you can tell me where to read about this or what method I could use to basically continue to be in charge of my body’s hormonal changes even without a uterus.
    Thank you so much 🙏🙏

    Reply
  10. Hi Laura,
    I’ve read that this treatment only Makes you bleed regularly but doesnt do anything to make you ovulate, is it true??

    Reply
    • Step one is to understand the difference between progesterone and progestins. Over time, cyclic progesterone can promote ovulation but progestins cannot. And even with micronised progesterone, the first few cycles are withdrawal bleeds, not ovulatory cycles.

      Reply
  11. Hi Lara, thank you so much for this information. I started this therapy after finding an article you wrote with Dr. Prior. It has truly given me my life back. How long do your patients stay on the protocol? When do you usually have patients try to stop taking the spironolactorne/progesterone combination? And do you have them stop in a phased approach or all at once?

    Reply
  12. Thank you for bringing hope to us with PCOS. So frustrating that the only answer is take the bc pill. I will email for a pdf copy of your paper!

    Reply
    • Hola Lara, muy interesante y le voy a proponer a mi ginecologa.
      Lo que si tengo una duda..yo hace años tuve sindrome de ovorios poliquisticos y tome anticonceptivos con dosis altas de hormonas, despues de años arranque de vuelta con pastillas porque nuevamente me dio ovarios poliquisticos,me hice el control despues de 6 meses de pastillas y los quistes desaparecieron, pero tengo miedo que vuelva ocurrir…seria correcto que tome progesterona ciclica?tengo mucho hirsutismo.

      Reply
  13. Sorry if this is not were I should post this question/comment
    I have a question concerning progesteron cream for hypothalamic amenorrhea. (this woman has had HA for more than 10 years and even after gaining 20 pounds and now above ideal weight, still HA) No signs of menopause in bloodwork.
    She got advised to take 1 pump of estrogel daily and progesteron cream 2 weeks on , 2 weeks off, but when should she start and stop if she is not ovulating?
    She did not start the estrogel because she really doesn’t want to take it (because of the issues she had with the pill and Mirena when she was younger), but she did start the progestogel daily because she doesn’t exactly knows when to start/stop since there are no signs of ovulation.
    She has been doing this for over 3 months now. The only thing she thinks could be a sign of ovulation is some discomfort/pain that reminds her of the ovulation pain she had when she was younger.
    She had very regular periods (which always lasted 7 – 8 days) but with very heavy bleeding on the first 2 – 3 days and then some. That is also why she always used to have iron deficiency.
    I have read your books, and advised them to her of course but I couldn’t find the answer on the progestogel use.
    I would really appreciate your advise / comment on this.
    Thank you.

    Reply
  14. This is amazing! I was wondering if you would recommend using natural over the counter progesterone cream for cyclic progesterone therapy or maybe it’s not ideal, but would it still work? And if so, what dosage would you recommend for the cream (standard dosage is 20mg I believe)?

    Reply
  15. Hi Dr. Briden! Great post, thank you!
    Is it safe to take progesterone when LH is not high? I have PCOs, insulin resistance and normal weight. In addition, I am struggling with insomnia.Could you bring some thoughts on that, please?

    Reply
    • Progesterone is most suited when there are anovulatory cycles and clear signs of androgen excess, like hirsutism. Is that your situation?

      Reply
      • Yes, for sure. Besides hirsutism, I have acne and hair loss. Thank you very much for your reply! I have been following your work for several years and it has been helped me a lot.

        Reply
  16. I have PCOS, insulin resistance and have not taken birth control for 4 years. However, my LH is not high. I often can’t control the androgens with supplements and diet alone, so I take spironolactone. Spironolactone makes my cycle irregular. Is it safe to take progesterone in this case ( mainly with respect to LH)?

    Reply
  17. Hi Dr Briden. I am 45 and definitely in the beginning stages of perimenopause. I have never been able to get pregnant and have endometriosis. I recently started taking Prometrium at 100mg a day for perimenopause symptoms. I read as one of the warnings that progesterone may have an effect on dementia. Would love to know your thoughts and if there is any evidence of a connection to dementia. Alzheimer’s is on both sides of my family. Part of me is very hesitant to take it and would love to know more.

    Thank you so much,
    Ruth

    Reply
    • The warnings are the Prometrium packet are for progestins, not progesterone. Which does create confusion and misses the whole point of progesterone being safer than progestins.
      As for brain health specifically, I am not aware of any evidence that progesterone is bad for brain health. Quite the opposite. According to a recent paper From Menopause to Neurodegeneration-Molecular Basis and Potential Therapy, progesterone is good for the brain and “the neuroprotective effects of progesterone are well known.”

      Reply
    • if capsules cannot be obtained, then cream is better than nothing.
      But keep in mind that cream cannot think the uterine lining or reliably produce a withdrawal bleed.

      Reply
  18. Hello my 17 daughter is having an awful time with PCOS . Three month bleeds , weight gain , hirsutism . She has chronic IBS which is much worse during her period .
    Can you get natural progesterone in Uk ? What kind of Dr do I go to , to get it prescribed ?

    Reply
  19. Hi I just have a very quick question for Lara
    In Peri menopause when using oestrogen therapy also would you recommend or ever use 200mg of utrogestan for 21 days over 300mg for 14?
    If so or not advantages/disadvantages?

    Reply
    • In perimenopause, the advantage of more continuous dosing of progesterone is that it can relieve symptoms like nights sweats, insomnia and migraines. Cyclic dosing is more important for younger women who are still trying to establish ovulation.

      Reply
      • Thank you. Is the 21 day regime @200mg a good place to start as I need to have a bleed to rid the endometrium still been having issues with 14 days as the bleed happens on second week instead of the week after, also I’m much more rounded and calmer on the progesterone days
        I guess with the 21 day regime I could potentially taper down the oestrogen part also in time if suited

        Reply
  20. Thanks very much for this and all your other articles and books – incredibly informative.

    I have been diagnosed with PCOS on the basis of polycystic ovaries on ultrasound, and visible hirsutism. I have regular cycles for a few months, then they go awry, and then normalise again. I track my LH with a Mira fertility device and my LH follows a normal level and pattern (one spike mid month). All androgens (free testosterone, androstenedione, DHEAS, DHT) have been tested and are actually on the low side – despite the visible hirsutism. Fasting insulin is less than 2.
    I have worked out that estrogen seems to cause some symptoms/inflammation. And that prolactin tends to rise a little bit with rising estrogen (but not out of range). So I’m trying to work out if using cyclical progesterone could help to maintain my cycles, and restore them when they become elongated? I’m not sure it applies to the type of PCOS I have – because my LH is normal -but would love to know your thoughts on whether cyclical progesterone might help in this situation?
    Thanks very much for any thoughts and all your knowledge sharing – your books have changed my life!

    Reply
    • Low fasting insulin suggests you might not be eating enough to achieve regular ovulation. It could be a situation of hypothalamic amenorrhea (undereating) with hirsutism.

      Reply
    • It depends on whether you’re seeing a period with the IUD or not. If yes, then the dosing is the same: cyclic until ovulation is established, then switch to taking it in the luteal phase. (You can identify the luteal phase by tracking temperatures.)

      Reply
    • With my patients, if the starting place is anovulatory cycles, I usually suggest taking it for a few months cyclically and then start tracking BBTs to try to detect ovulation and then change to starting the progesterone 2 days after the temperature rise.

      Reply
  21. My daughter is 14 and 4 months. She got her period for the first time at 13.5 exactly in December of 2020 and never again. It was heavy and heavy for long, at least a week. Endocrinologist checked all hormones and everything was normal. What can be the reason and should we be concerned? She has scoliosis, takes an ADD medication and is thin. Otherwise healthy.

    Reply
    • I’m in the same boat except my daughter is now 16. One normal period and nothing ever again. She was put on progesterone (not the bio-identical type) but after reading Lara’s book, I took her off and she’s been following her protocol for three months and nothing yet. We have no idea what to do. I’m not even sure I can find a doctor willing to prescribe this.

      Reply
  22. Hi Dr Briden,

    I started oral compounded bio-identical progesterone 4 months ago taking 100 mg on day 9-14 of my cycle and 200 mg on days 14 – the day I start my period. It has greatly improved my mood, but it has caused horrible acne. The acne gets worse and my eyebrows and eyelashes will fall out when I start taking 200 mg. I see a functional MD who put me on a high dose of fish oil but it hasn’t helped. I feel like I’m missing something. Any ideas?

    Reply
  23. Hi Lara , my daughter is taking 1000 mg Vit E every alternate day for last one monthas I read somewhere that it mimics progesterone, we do have noticed less facial growth , she is also taking 2 mg fish oil since last 4 months which has stopped her sneezing completely ,her insulin glucose test was 17 , one and a half year ago it was 24 , doctors say she has no insulin resistance issue ,her shbg has always been low,is that okay , kind regards , meena

    Reply
  24. Would taking it non cyclically cause any damage/problem? I take 300mg everyday with one pump of estrogel for peri menopause (I had pcos and fibroids etc prior to this stage of my life) symptoms. I am still not quite the full ticket so do you think it is having utrogestan daily that is holding me back?

    Reply
    • it’s fine to take progesterone daily in perimenopause. The main purpose of cyclic dosing is to try to establish ovulation. Since ovulation is unlikely in the later phases of perimenopause, then daily dosing can be fine.

      Reply
  25. Once cycles are ovulatory, should progesterone be given on day 14, even for women who tend to ovulate late, or should it be given only after ovulation has occurred? I will email for the PDF of your paper, I’m looking forward to reading it.

    Also, anecdotally, a lot of women seem to claim their hair loss issues are worsened by progesterone supplementation? Have you seen this happen in your practice? Is there any hope progesterone could improve or stabilize hair loss?

    Reply
    • Only after ovulation. So, if the follicular phase is longer, then progesterone will need to be started later. For patients who are only sometimes ovulating, I say something like: “Start progesterone 2 days after ovulation or day 21, whichever comes first.”

      Progesterone is beneficial for hair. Remember the 3 to 4-month lag-time for hair loss. If hair loss is observed, it’s because of something that happened 3 or 4 months before, such as stopping the pill for example.

      Reply

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