Femara or Clomid for Ovulation Induction?

Summary: If you are not ovulating naturally even after working on recovery, and want to use medication to induce ovulation for pregnancy, Femara (letrozole) is preferable to Clomid (clomiphene)*.




Letrozole, By MindZiper – Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=15991603


In No Period. Now What? (NPNW), our book on hypothalamic amenorrhea recovery, Chapter 21 covers the oral medications that can be used to encourage ovulation. We discuss how soy isoflavones, Femara, Clomid, and tamoxifen reduce estrogen levels to encourage an increase in follicle-stimulating hormone (FSH) that in turn leads to growth and maturation of eggs. These medications can be used when pregnancy is desired, but also to “jump-start” menstrual cycles*. It is really important to note that these meds are unlikely to work without progress having made toward recovery in the form of increased eating, reduced exercise, and reduced psychological stress – all of which you can read about in earlier sections in our book.




Clomiphene, by MarinaVladivostok (Own work) [CC0], via Wikimedia Commons



We also cover research comparing pregnancy rates, likelihood of a multiple-gestation pregnancy, uterine lining thickness, and other metrics between Femara (letrozole) and Clomid (clomiphene citrate) to help women decide which choice is optimal for them. (Tamoxifen is an alternate that is rarely used, so there is not a large body of research to reference, although in many ways it is preferable to Clomid based on fewer effects on the uterine lining.) We also discuss dosing recommendations, what to do if the first cycle doesn’t work, and much more. 🙂

Our conclusion in NPNW is that if one is trying to get pregnant, Continue reading

Resources for understanding hypothalamic amenorrhea versus PCOS

When you have no period, there is a standard workup doctors will do to try and determine the cause. They should do a physical exam, take a history and probably do some bloodwork. It is also fairly common to have a pelvic ultrasound.

When a woman with a history suggesting hypothalamic amenorrhea goes for an ultrasound, I warn her that it is common to see many small follicles (also called “cysts”) on her ovaries. That can lead to a doctor calling the ovaries “polycystic” and suggesting polycystic ovarian syndrome (PCOS) as a diagnosis.  As we described in our earlier post about HA versus PCOS, absent periods and ovaries with a lot of follicles are not sufficient to diagnose PCOS, especially with a history that points more toward hypothalamic amenorrhea.

We put together an information sheet to summarize the differences between hypothalamic amenorrhea and PCOS to help you and your doctors determine which is the correct diagnosis for you. In addition, we’re making the sixth chapter of No Period. Now What? (The HA/PCOS conundrum) available for download. This chapter not only discusses diagnosing HA and PCOS but also what might happen if you have both HA and PCOS, as well as some ideas for PCOS treatment and long-term concerns if you do in fact have PCOS. Enter your email address to receive an email with a download link for both. Please feel free to share the files: for example with your doctors and other women with HA/”lean” PCOS.



Hope this helps!!  Any questions, please comment on this post or use the contact form!


In case you’re interested, references for the information sheet are listed below.

Hypothalamic Amenorrhea versus PCOS Information Sheet References

Diagnosing PCOS:

  • Johnson TRB, et al. “Evidence-Based Methodology Workshop on Polycystic Ovary
    Syndrome.” Bethesda, Maryland: National Institutes of Health, 2012. http://prevention.nih.gov/workshops/2012/pcos/docs/FinalReport.pdf
  • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
    “Revised 2003 Consensus on Diagnostic Criteria and Long-term Health Risks Related
    to Polycystic Ovary Syndrome (PCOS).” Human Reproduction. 19(1) 2004: 41-47. doi:

Diagnosing polycystic ovaries:

  • Balen AH, et al. “Ultrasound Assessment of the Polycystic Ovary: International
    Consensus Definitions.” Human Reproduction Update. 9(6) 2003: 505-14. doi: 10.1093/
  • Dewailly D, et al. “Definition and Significance of Polycystic Ovarian Morphology:
    A Task Force Report from the Androgen Excess and Polycystic Ovary Syndrome Society.”
    Human Reproduction Update. 20(3) 2014: 334-52. doi: 10.1093/humupd/dmt061
  • Lujan ME, et al. “Updated Ultrasound Criteria for Polycystic Ovary Syndrome:
    Reliable Thresholds for Elevated Follicle Population and Ovarian Volume.” Human
    Reproduction. 28(5) 2013: 1361-368. doi: 10.1093/humrep/det062


  • Liang SJ, et al. “Clinical and Biochemical Presentation of Polycystic Ovary Sydrome
    in Women between the Ages of 20 and 40.” Human Reproduction. 26(12) 2011: 3443-
    449. doi: 10.1093/humrep/der302
  • Azziz R, et al. “The Prevalence and Features of the Polycystic Ovary Syndrome in
    an Unselected Population.” The Journal of Clinical Endocrinology & Metabolism. 89(6)
    2004: 2745-749. doi: 10.1210/jc.2003-032046
  • Azziz R, et al. “Criteria for Defining Polycystic Ovary Syndrome as a Predominantly
    Hyperandrogenic Syndrome: An Androgen Excess Society Guideline.” The Journal of
    Clinical Endocrinology & Metabolism. 91(11) 2006: 4237-245. doi: 10.1210/jc.2006-0178
  • Sivayoganathan D, et al. “Full Investigation of Patients with Polycystic Ovary Syndrome
    (PCOS) Presenting to Four Different Clinical Specialties Reveals Significant
    Differences and Undiagnosed Morbidity.” Human Fertility. 14(4) 2011: 261-65. doi:
  • Ferriman D, Gallwey JD. “Clinical Assessment Of Body Hair Growth In Women.”
    The Journal of Clinical Endocrinology & Metabolism. 21(11) 1961: 1440-447. doi: 10.1210/jcem-21-11-1440
  • Kar, S. “Anthropometric, Clinical, and Metabolic Comparisons of the Four Rotterdam
    PCOS Phenotypes: A Prospective Study of PCOS Women.” Journal of Human
    Reproductive Sciences. 6(3) 2013: 194. doi: 10.4103/0974-1208.121422
  • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
    2004. doi: 10.1093/humrep/deh098

Multi-cystic ovaries in women with hypothalamic amenorrhea:

  • Robin G, et al. “Polycystic Ovary-Like Abnormalities (PCO-L) in Women with
    Functional Hypothalamic Amenorrhea.” The Journal of Clinical Endocrinology & Metabolism.
    97(11) 2012: 4236-243. doi: 10.1210/jc.2012-1836
  • Falsetti, L. “Long-term Follow-up of Functional Hypothalamic Amenorrhea and
    Prognostic Factors.” The Journal of Clinical Endocrinology & Metabolism. 87(2) 2002):
    500-05. doi: 10.1210/jcem.87.2.8195

Hypothalamic amenorrhea or PCOS???

When you have no period and are trying to figure out why, it is important to determine whether you have hypothalamic amenorrhea or PCOS, and the two are often confused. (See this post for additional resources, including a free downloadable information sheet and the “HA/PCOS Conundrum” chapter of No Period. Now What?)

The World Health Organization has three classifications for infertility associated with anovulation and amenorrhea. Group I comprises those with low gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone (FSH)) and estrogen, Group II consists of women with normal gondadotropins/estrogen, Group III is women with increased gonadotropins (e.g. in perimenopause).

In typical hypothalamic amenorrhea, which is essentially what the WHO Group I describes, LH is low, often less than 2 IU/L, as you can see in this figure showing LH levels in 45 women when they were diagnosed with hypothalamic amenorrhea. Note that the two women with LH values > 10 were further investigated for possible PCOS.

LH in women with hypothalamic amenorrhea

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